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Papers by P. Bie

Research paper thumbnail of Normotension, hypertension and body fluid regulation: brain and kidney

Acta Physiologica, 2016

The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowl... more The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowledge of mechanisms of secondary hypertension increases, but in most new cases of hypertension the pathophysiology remains unknown. Separate neurocentric and renocentric concepts of aetiology have prevailed without much interaction. In this regard, several questions regarding the relationships between body fluid and blood pressure regulation are pertinent. Are all forms of EH associated with sympathetic overdrive or a shift in the pressure-natriuresis curve? Is body fluid homoeostasis normally driven by the influence of arterial blood pressure directly on the kidney? Does plasma renin activity, driven by renal nerve activity and renal arterial pressure, provide a key to stratification of EH? Our review indicates that (i) a narrow definition of EH is useful; (ii) in EH, indices of cardiovascular sympathetic activity are elevated in about 50% of cases; (iii) in EH as in normal conditions, mediators other than arterial blood pressure are the major determinants of renal sodium excretion; (iv) chronic hypertension is always associated with a shift in the pressure-natriuresis curve, but this may be an epiphenomenon; (v) plasma renin levels are useful in the analysis of EH only after metabolic standardization and then determination of the renin function line (plasma renin as a function of sodium intake); and (vi) angiotensin II-mediated hypertension is not a model of EH. Recent studies of baroreceptors and renal nerves as well as sodium intake and renin secretion help bridge the gap between the neurocentric and renocentric concepts.

Research paper thumbnail of Effects of Atrial Natriuretic Peptides and Furosemide in Conscious Dogs

Experimental Biology and Medicine, 1987

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diur... more Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.

Research paper thumbnail of expansion in compensated heart failure Neuroendocrine and renal effects of intravascular volume

Research paper thumbnail of Activation of RAAS in a rat model of liver cirrhosis: no effect of losartan on renal sodium excretion

BMC Nephrology, 2018

Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the... more Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis. Methods: Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured. Results: The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p < 0.001) which indicated hemodynamic impairment. Conclusions: Losartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.

Research paper thumbnail of Renal effects of overhydration during vasopressin infusion in conscious dogs

American Journal of Physiology-Renal Physiology, 1984

The antidiuretic and possibly natriuretic effects of small doses of vasopressin (AVP) were invest... more The antidiuretic and possibly natriuretic effects of small doses of vasopressin (AVP) were investigated in conscious dogs. Plasma composition and renal excretion of water, Na+, and K+ were measured after overhydration by 20 ml/kg performed during infusion of AVP at rates of 50, 100, 150, 200, or 400 pg X min-1 X kg body wt-1 or of 1-desamino-8-D-arginine vasopressin (DDAVP) 50 pg X min-1 X kg body wt-1. Hydration lowered plasma osmolality and sodium concentration by 4.2 +/- 0.3 and 3.8 +/- 0.2%, respectively; plasma protein showed a larger decrease, 8.5 +/- 0.4% (P less than 0.01). Urine osmolality during hydration was 52 +/- 3 mosmol/kg H2O. AVP infusion at 100 pg X min-1 X kg-1 elevated plasma vasopressin by 1.7 +/- 0.3 pg/ml and urine osmolality by 1,049 +/- 152 mosmol/kg H2O and elicited marked natriuresis and kaliuresis but no change in osmolar clearance. During DDAVP infusion urine osmolality was 1,365 +/- 134 mosmol/kg H2O, but electrolyte excretion was indistinguishable from...

Research paper thumbnail of Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

American Journal of Physiology-Endocrinology and Metabolism, 1982

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopres... more The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intr...

Research paper thumbnail of Hormonal regulation of renal sodium and water excretion during normotensive sodium loading in conscious dogs

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three dif... more Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 µmol • kg Ϫ1 • min Ϫ1) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 µmol • kg Ϫ1 • min Ϫ1. During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14 Ϯ 2 to 7 Ϯ 2 pg/ml and sodium excretion increased markedly (2.3 Ϯ 0.8 to 19 Ϯ 8 µmol/min), whereas glomerular filtration rate (GFR) remained constant. Iso-Load-20 decreased plasma ANG II similarly (13 Ϯ 3 to 7 Ϯ 1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9 Ϯ 1.0 to 11 Ϯ 6 µmol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mmHg and decreased plasma ANG II to ϳ6 pg/ml, whereas sodium excretion increased to ϳ60 µmol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry. angiotensin II; volume expansion; vasopressin; blood pressure; natriuresis.

Research paper thumbnail of Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans

American Journal of Physiology-Heart and Circulatory Physiology, 2001

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostati... more We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (−22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 ± 1 mmHg, P < 0.05) and less during WI + NS (4 ± 1 mmHg) and NS (3 ± 1 mmHg). The decrease in heart rate (HR) by 13 ± 1 beats/min ( P < 0.05) and the increase in arterial pulse pressure (PP) by 17 ± 4 mmHg ( P< 0.05) during supine was more pronounce...

Research paper thumbnail of Determinants of the natriuresis after acute, slow sodium loading in conscious dogs

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000

The relative importance of systemic volume, concentration, and pressure signals in sodium homeost... more The relative importance of systemic volume, concentration, and pressure signals in sodium homeostasis was investigated by intravenous infusion of isotonic (IsoLoad) or hypertonic (HyperLoad) saline at a rate (1 μmol Na+⋅ kg−1⋅ s−1), similar to the rate of postprandial sodium absorption. IsoLoad decreased plasma vasopressin (−35%) and plasma ANG II (−77%) and increased renal sodium excretion (95-fold), arterial blood pressure (ΔBP; +6 mmHg), and heart rate (HR; +36%). HyperLoad caused similar changes in plasma ANG II and sodium excretion, but augmented vasopressin (12-fold) and doubled ΔBP (+12 mmHg) without changing HR. IsoLoad during vasopressin clamping (constant vasopressin infusion) caused comparable natriuresis at augmented ΔBP (+14 mmHg), but constant HR. Thus vasopressin abolished the Bainbridge reflex. IsoLoad during normotensive angiotensin clamping (enalaprilate plus constant angiotensin infusion) caused marginal natriuresis (9% of unclamped response) despite augmented ΔBP...

Research paper thumbnail of Osmoreceptors, vasopressin, and control of renal water excretion

Physiological Reviews, 1980

October 1980 OSMORECEPTORS AND RENAL WATER EXCRETION 963 found that the kidney secreted large amo... more October 1980 OSMORECEPTORS AND RENAL WATER EXCRETION 963 found that the kidney secreted large amounts of dilute urine unless postpituitary extract was added to-or the head of a dog included in-the perfusion circuit. The significance of these observations was greatly increased by the work of Klisiecki et al. (254,255). Using conscious, chronically prepared dogs they made a series of pertinent observations on water absorption and excretion and concluded their work with a statement that has withstood the test of time: The secretion of water, over and above that required for the solutes of the urine, is conditioned by and dependent upon a fall in the concentration in blood and kidney of the antidiuretic principle of the pituitary body. The secretion of the antidiuretic principle is itself controlled, through the intermediation of the nervous system, by the concentration of water in blood and tissues.

Research paper thumbnail of Lithium clearance in dogs: effects of water loading, amiloride and lithium dosage

Clinical Science, 1992

1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the... more 1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the renal handling of lithium in normal conscious dogs were investigated. 2. Lithium was administered in the diet at daily doses of 100 mg or 2 mg of lithium carbonate for the 2 days preceding the investigation. Urine flow rate was altered by water loading with and without arginine vasopressin infusion (5 pg min−1 kg−1). Amiloride was administered as an intravenous bolus (130 μg/kg) followed by a continuous infusion (1.22 μg h−1 kg−1). 3. Glomerular filtration rate (exogenous creatinine clearance) did not change within series and was not different between series; it averaged 3.27 ml min−1 kg−1. Control levels of fractional lithium excretion (12.4 ± 1.2%, mean ± sem) were not influenced by hydration, hydration plus arginine vasopressin administration or the lithium dosage. However, in hydrated dogs having a plasma lithium concentration of 130–140 μmol/l, amiloride administration was associat...

Research paper thumbnail of P0094 : Impaired 11β-hydroxysteroid dehydrogenase type 2 activity contributes to renal sodium avidity in human cirrhosis

Journal of Hepatology, 2015

Research paper thumbnail of Effect of Osmotic Stimuli on the Concentration of Vasopressin in Jugular and Peripheral Venous Plasma

Kidney and Body Fluids, 1981

Publisher Summary The relation between the rate of secretion of vasopressin and the osmolality of... more Publisher Summary The relation between the rate of secretion of vasopressin and the osmolality of the body fluids is a basic element of the extracellular fluid homeostasis. The chapter presents experiments conducted on conscious, euhydrated dogs, which evaluate the effect of short, bilateral, and intracarotid infusions of hypertonic saline on the concentrations of vasopressin in jugular and systemic plasma. The results show that (1) infusions of hypertonic saline bilaterally into the common carotid arteries are associated with an increase in the concentration of vasopressin in plasma, (2) intravenous administration of identical, hypertonic solutions are ineffective - or at least much less effective - in eliciting the release of vasopressin, and (3) the difference between the concentration of vasopressin in jugular venous plasma and the concentration in venous plasma from a hind leg is small and statistically demonstrable only in some of the animals. The mechanisms responsible for the control of the secretion of vasopressin normally maintain a delicate balance sensitive to stimuli, which are part of homeostatic systems and to perturbations, which a priori would have appeared less likely to influence the secretion of this hormone..

Research paper thumbnail of Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man

Clinical Physiology, 1988

Circulatory variables and hormone concentrations in arterial plasma were measured in six normal s... more Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin I1 (ANG 11) step-up infusion of 0.25 and 1.00 ng kg-' x min. During the 1-00 ng kg-' x min infusion A N G I1 plasma concentrations increased from 11 f 2 to 48 f 6 pg ml-I; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P<0.05) from a resting value of 8 9 f 3 to 9 7 f 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P<0-05) from 36 2 4 to 77 f 10 pg ml-' during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-' x min infusion subcutaneous blood flow decreased (P = 0.06) to 67 2 20 and 66 2 26%, respectively, of control. It is concluded that: (1) A N G I1 in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) A N G I1 does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG I1 do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma A N G 11.

Research paper thumbnail of Determination of local catecholamine release by microdialysis

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1993

Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in c... more Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in combination with an ultrasensitive radio-enzymatic noradrenaline assay. Experiments were performed in conscious dogs with and without tyramine added to the perfusion medium. In the absence of tyramine, the interstitial noradrenaline levels in subcutaneous tissue were similar to arterial blood concentrations provided the former were corrected for recovery. With tyramine added to the perfusion medium, noradrenaline levels in subcutaneous tissue increased tenfold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. In four healthy males, the subcutaneous dialysate noradrenaline concentration increased during cold exposure by a factor of 3.5 (Friedman test, P < 0.003). Skin temperature decreased by an average of -12 degrees C +/- 0.6 degrees C during cold exposure. The microdialysis technique in combination with a sen...

Research paper thumbnail of Effects of a Low Sodium Diet with a High Potassium Content on Plasma Endothelin-1, Atrial Natriuretic Peptide and Arginine Vasopressin in Normal Dogs

Journal of Veterinary Medicine Series A, 1994

Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and afte... more Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and after this period the dogs received a control diet for 3 weeks. Both diets provided the dogs with approximately 6.8 mmol K+ /kg/day. Neither introducing nor withdrawing the low sodium diet changed the plasma concentrations of endothelin-1 (ET-l), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). Pooled data from the control periods were not different from thelow sodiumperiodforeither ET-1 (2.31 pg/mland2.09 pg/ml, P = 0.21), ANP(42.51 pg/ml and 38.99 pg/ml, P = 0.44) or AVP (4.14 pg/ml and 4.16 pg/ml, P = 0.91). It was concluded that ET-1, ANP and AVP in normal dogs are unaffected by a 6-fold change in sodium intake in the presence of a high potassium intake.

Research paper thumbnail of FEPS congresses, a concept with a future?

Pfl�gers Archiv European Journal of Physiology, 2001

Research paper thumbnail of Unexpected renal responses in space

The Lancet, 2000

Urine output in astronauts following ingestion of an oral water load was low in space on the Russ... more Urine output in astronauts following ingestion of an oral water load was low in space on the Russian space station Mir and less than during simulation by 6°head-down bed rest. This surprising observation shows that the effects of gravity and weightlessness on fluid volume regulation are not well understood and that the head-down bed-rest model does not simulate the effects of weightlessness on renal water handling.

Research paper thumbnail of Effect of Posture on the Plasma Concentration of Immunoreactive Human Natriuretic Peptide (p-iANP)

Journal of Cardiovascular Pharmacology, 1986

Research paper thumbnail of The influence of high and low levels of estrogen on diurnal urine regulation in young women

BMC Urology, 2008

Background: Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on... more Background: Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21-33 y) underwent two circadian in-patient investigations, both situated in follicular phase. Methods: Admitting the participants solely in the follicular phase resulted in high and low plasmaestradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP), urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2) and aquaporin-2 (AQP-2). Blood pressure was measured every hour. Results: Plasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions. Conclusion: High and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP release. Furthermore it appears that oxytocin under normal physiological conditions do not contribute to the overall antidiuretic effect.

Research paper thumbnail of Normotension, hypertension and body fluid regulation: brain and kidney

Acta Physiologica, 2016

The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowl... more The fraction of hypertensive patients with essential hypertension (EH) is decreasing as the knowledge of mechanisms of secondary hypertension increases, but in most new cases of hypertension the pathophysiology remains unknown. Separate neurocentric and renocentric concepts of aetiology have prevailed without much interaction. In this regard, several questions regarding the relationships between body fluid and blood pressure regulation are pertinent. Are all forms of EH associated with sympathetic overdrive or a shift in the pressure-natriuresis curve? Is body fluid homoeostasis normally driven by the influence of arterial blood pressure directly on the kidney? Does plasma renin activity, driven by renal nerve activity and renal arterial pressure, provide a key to stratification of EH? Our review indicates that (i) a narrow definition of EH is useful; (ii) in EH, indices of cardiovascular sympathetic activity are elevated in about 50% of cases; (iii) in EH as in normal conditions, mediators other than arterial blood pressure are the major determinants of renal sodium excretion; (iv) chronic hypertension is always associated with a shift in the pressure-natriuresis curve, but this may be an epiphenomenon; (v) plasma renin levels are useful in the analysis of EH only after metabolic standardization and then determination of the renin function line (plasma renin as a function of sodium intake); and (vi) angiotensin II-mediated hypertension is not a model of EH. Recent studies of baroreceptors and renal nerves as well as sodium intake and renin secretion help bridge the gap between the neurocentric and renocentric concepts.

Research paper thumbnail of Effects of Atrial Natriuretic Peptides and Furosemide in Conscious Dogs

Experimental Biology and Medicine, 1987

Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diur... more Effects of ANF(8-33) and Auriculin A on renal variables were investigated in conscious water-diuretic dogs. The two substances were injected intravenously (1.08 micrograms/kg in 3 min) or ANF(8-33) was infused (0.2 microgram/kg X min in 20 min). The effects were compared to those of an equinatriuretic dose of furosemide (1.0 microgram/kg X min). Injections caused increases in sodium excretion, diuresis, and osmolar clearance. No significant change in exogenous creatine clearance (CCREA) occurred. Infusion of ANF(8-33) decreased blood pressure by 14% (P less than 0.01) and increased sodium excretion by a factor of 10 (P less than 0.01). The natriuresis was a function of increases in diuresis and urinary sodium concentration, the latter by a factor of 6 (P less than 0.01). Diuresis and free-water clearance (CH2O) increased by 60% (P less than 0.01), but urine osmolality did not change significantly. After the infusion a significant decrease in PAH clearance (CPAH) (P less than 0.01) was observed. Filtration fraction (FF) did not change. The furosemide natriuresis appeared later than that of ANF without significant deviations in diuresis, CH2O, CCREA, CPAH, and FF; urine osmolality increased by 35% (P less than 0.01). The effects of ANF(8-33) differ from those of furosemide in several ways. First, the onset of natriuresis is faster, second, the natriuresis is associated by marked increases in diuresis and free-water clearance but not in urine osmolality; and third, natriuresis is followed by a reduction in renal blood flow. The rapid natriuresis of ANF can occur without changes in glomerular filtration rate.

Research paper thumbnail of expansion in compensated heart failure Neuroendocrine and renal effects of intravascular volume

Research paper thumbnail of Activation of RAAS in a rat model of liver cirrhosis: no effect of losartan on renal sodium excretion

BMC Nephrology, 2018

Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the... more Background: Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis. Methods: Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured. Results: The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p < 0.001) which indicated hemodynamic impairment. Conclusions: Losartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.

Research paper thumbnail of Renal effects of overhydration during vasopressin infusion in conscious dogs

American Journal of Physiology-Renal Physiology, 1984

The antidiuretic and possibly natriuretic effects of small doses of vasopressin (AVP) were invest... more The antidiuretic and possibly natriuretic effects of small doses of vasopressin (AVP) were investigated in conscious dogs. Plasma composition and renal excretion of water, Na+, and K+ were measured after overhydration by 20 ml/kg performed during infusion of AVP at rates of 50, 100, 150, 200, or 400 pg X min-1 X kg body wt-1 or of 1-desamino-8-D-arginine vasopressin (DDAVP) 50 pg X min-1 X kg body wt-1. Hydration lowered plasma osmolality and sodium concentration by 4.2 +/- 0.3 and 3.8 +/- 0.2%, respectively; plasma protein showed a larger decrease, 8.5 +/- 0.4% (P less than 0.01). Urine osmolality during hydration was 52 +/- 3 mosmol/kg H2O. AVP infusion at 100 pg X min-1 X kg-1 elevated plasma vasopressin by 1.7 +/- 0.3 pg/ml and urine osmolality by 1,049 +/- 152 mosmol/kg H2O and elicited marked natriuresis and kaliuresis but no change in osmolar clearance. During DDAVP infusion urine osmolality was 1,365 +/- 134 mosmol/kg H2O, but electrolyte excretion was indistinguishable from...

Research paper thumbnail of Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

American Journal of Physiology-Endocrinology and Metabolism, 1982

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopres... more The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intr...

Research paper thumbnail of Hormonal regulation of renal sodium and water excretion during normotensive sodium loading in conscious dogs

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three dif... more Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 µmol • kg Ϫ1 • min Ϫ1) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 µmol • kg Ϫ1 • min Ϫ1. During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14 Ϯ 2 to 7 Ϯ 2 pg/ml and sodium excretion increased markedly (2.3 Ϯ 0.8 to 19 Ϯ 8 µmol/min), whereas glomerular filtration rate (GFR) remained constant. Iso-Load-20 decreased plasma ANG II similarly (13 Ϯ 3 to 7 Ϯ 1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9 Ϯ 1.0 to 11 Ϯ 6 µmol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mmHg and decreased plasma ANG II to ϳ6 pg/ml, whereas sodium excretion increased to ϳ60 µmol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry. angiotensin II; volume expansion; vasopressin; blood pressure; natriuresis.

Research paper thumbnail of Cardiovascular effects of static carotid baroreceptor stimulation during water immersion in humans

American Journal of Physiology-Heart and Circulatory Physiology, 2001

We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostati... more We hypothesized that the more-pronounced hypotensive and bradycardic effects of an antiorthostatic posture change from seated to supine than water immersion are caused by hydrostatic carotid baroreceptor stimulation. Ten seated healthy males underwent five interventions of 15-min each of 1) posture change to supine, 2) seated water immersion to the Xiphoid process (WI), 3) seated neck suction (NS), 4) WI with simultaneous neck suction (−22 mmHg) adjusted to simulate the carotid hydrostatic pressure increase during supine (WI + NS), and 5) seated control. Left atrial diameter increased similarly during supine, WI + NS, and WI and was unchanged during control and NS. Mean arterial pressure (MAP) decreased the most during supine (7 ± 1 mmHg, P < 0.05) and less during WI + NS (4 ± 1 mmHg) and NS (3 ± 1 mmHg). The decrease in heart rate (HR) by 13 ± 1 beats/min ( P < 0.05) and the increase in arterial pulse pressure (PP) by 17 ± 4 mmHg ( P< 0.05) during supine was more pronounce...

Research paper thumbnail of Determinants of the natriuresis after acute, slow sodium loading in conscious dogs

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2000

The relative importance of systemic volume, concentration, and pressure signals in sodium homeost... more The relative importance of systemic volume, concentration, and pressure signals in sodium homeostasis was investigated by intravenous infusion of isotonic (IsoLoad) or hypertonic (HyperLoad) saline at a rate (1 μmol Na+⋅ kg−1⋅ s−1), similar to the rate of postprandial sodium absorption. IsoLoad decreased plasma vasopressin (−35%) and plasma ANG II (−77%) and increased renal sodium excretion (95-fold), arterial blood pressure (ΔBP; +6 mmHg), and heart rate (HR; +36%). HyperLoad caused similar changes in plasma ANG II and sodium excretion, but augmented vasopressin (12-fold) and doubled ΔBP (+12 mmHg) without changing HR. IsoLoad during vasopressin clamping (constant vasopressin infusion) caused comparable natriuresis at augmented ΔBP (+14 mmHg), but constant HR. Thus vasopressin abolished the Bainbridge reflex. IsoLoad during normotensive angiotensin clamping (enalaprilate plus constant angiotensin infusion) caused marginal natriuresis (9% of unclamped response) despite augmented ΔBP...

Research paper thumbnail of Osmoreceptors, vasopressin, and control of renal water excretion

Physiological Reviews, 1980

October 1980 OSMORECEPTORS AND RENAL WATER EXCRETION 963 found that the kidney secreted large amo... more October 1980 OSMORECEPTORS AND RENAL WATER EXCRETION 963 found that the kidney secreted large amounts of dilute urine unless postpituitary extract was added to-or the head of a dog included in-the perfusion circuit. The significance of these observations was greatly increased by the work of Klisiecki et al. (254,255). Using conscious, chronically prepared dogs they made a series of pertinent observations on water absorption and excretion and concluded their work with a statement that has withstood the test of time: The secretion of water, over and above that required for the solutes of the urine, is conditioned by and dependent upon a fall in the concentration in blood and kidney of the antidiuretic principle of the pituitary body. The secretion of the antidiuretic principle is itself controlled, through the intermediation of the nervous system, by the concentration of water in blood and tissues.

Research paper thumbnail of Lithium clearance in dogs: effects of water loading, amiloride and lithium dosage

Clinical Science, 1992

1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the... more 1. The influences of lithium dosage, urine flow rate and acute administration of amiloride on the renal handling of lithium in normal conscious dogs were investigated. 2. Lithium was administered in the diet at daily doses of 100 mg or 2 mg of lithium carbonate for the 2 days preceding the investigation. Urine flow rate was altered by water loading with and without arginine vasopressin infusion (5 pg min−1 kg−1). Amiloride was administered as an intravenous bolus (130 μg/kg) followed by a continuous infusion (1.22 μg h−1 kg−1). 3. Glomerular filtration rate (exogenous creatinine clearance) did not change within series and was not different between series; it averaged 3.27 ml min−1 kg−1. Control levels of fractional lithium excretion (12.4 ± 1.2%, mean ± sem) were not influenced by hydration, hydration plus arginine vasopressin administration or the lithium dosage. However, in hydrated dogs having a plasma lithium concentration of 130–140 μmol/l, amiloride administration was associat...

Research paper thumbnail of P0094 : Impaired 11β-hydroxysteroid dehydrogenase type 2 activity contributes to renal sodium avidity in human cirrhosis

Journal of Hepatology, 2015

Research paper thumbnail of Effect of Osmotic Stimuli on the Concentration of Vasopressin in Jugular and Peripheral Venous Plasma

Kidney and Body Fluids, 1981

Publisher Summary The relation between the rate of secretion of vasopressin and the osmolality of... more Publisher Summary The relation between the rate of secretion of vasopressin and the osmolality of the body fluids is a basic element of the extracellular fluid homeostasis. The chapter presents experiments conducted on conscious, euhydrated dogs, which evaluate the effect of short, bilateral, and intracarotid infusions of hypertonic saline on the concentrations of vasopressin in jugular and systemic plasma. The results show that (1) infusions of hypertonic saline bilaterally into the common carotid arteries are associated with an increase in the concentration of vasopressin in plasma, (2) intravenous administration of identical, hypertonic solutions are ineffective - or at least much less effective - in eliciting the release of vasopressin, and (3) the difference between the concentration of vasopressin in jugular venous plasma and the concentration in venous plasma from a hind leg is small and statistically demonstrable only in some of the animals. The mechanisms responsible for the control of the secretion of vasopressin normally maintain a delicate balance sensitive to stimuli, which are part of homeostatic systems and to perturbations, which a priori would have appeared less likely to influence the secretion of this hormone..

Research paper thumbnail of Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man

Clinical Physiology, 1988

Circulatory variables and hormone concentrations in arterial plasma were measured in six normal s... more Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin I1 (ANG 11) step-up infusion of 0.25 and 1.00 ng kg-' x min. During the 1-00 ng kg-' x min infusion A N G I1 plasma concentrations increased from 11 f 2 to 48 f 6 pg ml-I; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P<0.05) from a resting value of 8 9 f 3 to 9 7 f 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P<0-05) from 36 2 4 to 77 f 10 pg ml-' during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-' x min infusion subcutaneous blood flow decreased (P = 0.06) to 67 2 20 and 66 2 26%, respectively, of control. It is concluded that: (1) A N G I1 in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) A N G I1 does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG I1 do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma A N G 11.

Research paper thumbnail of Determination of local catecholamine release by microdialysis

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1993

Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in c... more Release of noradrenaline in subcutaneous tissue was measured using a microdialysis technique in combination with an ultrasensitive radio-enzymatic noradrenaline assay. Experiments were performed in conscious dogs with and without tyramine added to the perfusion medium. In the absence of tyramine, the interstitial noradrenaline levels in subcutaneous tissue were similar to arterial blood concentrations provided the former were corrected for recovery. With tyramine added to the perfusion medium, noradrenaline levels in subcutaneous tissue increased tenfold. Arterial noradrenaline concentrations did not change, indicating that noradrenaline was released only locally in the tissue. In four healthy males, the subcutaneous dialysate noradrenaline concentration increased during cold exposure by a factor of 3.5 (Friedman test, P < 0.003). Skin temperature decreased by an average of -12 degrees C +/- 0.6 degrees C during cold exposure. The microdialysis technique in combination with a sen...

Research paper thumbnail of Effects of a Low Sodium Diet with a High Potassium Content on Plasma Endothelin-1, Atrial Natriuretic Peptide and Arginine Vasopressin in Normal Dogs

Journal of Veterinary Medicine Series A, 1994

Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and afte... more Eight clinically healthy male beagle dogs received a low sodium diet for 5 weeks. Before and after this period the dogs received a control diet for 3 weeks. Both diets provided the dogs with approximately 6.8 mmol K+ /kg/day. Neither introducing nor withdrawing the low sodium diet changed the plasma concentrations of endothelin-1 (ET-l), atrial natriuretic peptide (ANP) and arginine vasopressin (AVP). Pooled data from the control periods were not different from thelow sodiumperiodforeither ET-1 (2.31 pg/mland2.09 pg/ml, P = 0.21), ANP(42.51 pg/ml and 38.99 pg/ml, P = 0.44) or AVP (4.14 pg/ml and 4.16 pg/ml, P = 0.91). It was concluded that ET-1, ANP and AVP in normal dogs are unaffected by a 6-fold change in sodium intake in the presence of a high potassium intake.

Research paper thumbnail of FEPS congresses, a concept with a future?

Pfl�gers Archiv European Journal of Physiology, 2001

Research paper thumbnail of Unexpected renal responses in space

The Lancet, 2000

Urine output in astronauts following ingestion of an oral water load was low in space on the Russ... more Urine output in astronauts following ingestion of an oral water load was low in space on the Russian space station Mir and less than during simulation by 6°head-down bed rest. This surprising observation shows that the effects of gravity and weightlessness on fluid volume regulation are not well understood and that the head-down bed-rest model does not simulate the effects of weightlessness on renal water handling.

Research paper thumbnail of Effect of Posture on the Plasma Concentration of Immunoreactive Human Natriuretic Peptide (p-iANP)

Journal of Cardiovascular Pharmacology, 1986

Research paper thumbnail of The influence of high and low levels of estrogen on diurnal urine regulation in young women

BMC Urology, 2008

Background: Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on... more Background: Sex hormones have a pronounced effect on arginine vasopressin (AVP), and therefore on the diurnal water homeostasis. Low and high levels of plasma-estradiol as seen in the follicular phase of the menstrual cycle may therefore alter the diurnal regulation of urine production. Furthermore the structural resemblance of oxytocin to vasopressin has led to speculations about the possible antidiuretic properties of oxytocin under normal physiological conditions. To elucidate the influence of high and low p-estradiol on the regulation of the diurnal urine production, 15 normal menstruating women (21-33 y) underwent two circadian in-patient investigations, both situated in follicular phase. Methods: Admitting the participants solely in the follicular phase resulted in high and low plasmaestradiol whereas plasma-progesterone was similar. Urine and blood samples were taken at predetermined time points to determine plasma AVP, plasma oxytocin, plasma aldosterone, plasma natriuretic peptide (ANP), urinary solute excretions, and urinary excretions of prostaglandin E2 (PGE-2) and aquaporin-2 (AQP-2). Blood pressure was measured every hour. Results: Plasma AVP, plasma aldosterone and plasma ANP were unaffected by the different levels of estradiol. All had marked circadian variations whereas oxytocin did not display any circadian rhythm. High estradiol resulted in lower p-osmolality and p-sodium reflecting the downward resetting of the osmoreceptors. Oxytocin did not correlate with either diuresis or urine osmolality. The diurnal urine production was similar in the two groups as were urine osmolality, excretion of PGE-2 and AQP-2. AQP-2 does not have a circadian rhythm and is not significantly correlated to either AVP or oxytocin under normal physiological conditions. Conclusion: High and low level of estradiol has no influence on the circadian rhythm of AVP or the subsequent urine production. High p-estradiol resets the osmoreceptors for AVP release. Furthermore it appears that oxytocin under normal physiological conditions do not contribute to the overall antidiuretic effect.