Ilkka Pörsti - Academia.edu (original) (raw)

Papers by Ilkka Pörsti

Research paper thumbnail of Penetration of some compounds through blood-brain and blood-testis barriers in chronically hypertensive rats

Acta Physiologica Scandinavica, 1984

Research paper thumbnail of AT1 Receptor Blockade Improves Vasorelaxation in Experimental Renal Failure

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and... more It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular synthesis

Research paper thumbnail of Effects of oxonic acid-induced hyperuricemia on mesenteric artery tone and cardiac load in experimental renal insufficiency

BMC Nephrology, 2015

Background: Recent studies suggest a causal role for increased plasma uric acid in the progressio... more Background: Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). However, uric acid also functions as an antioxidant with possible beneficial effects. Methods: We investigated the influence of hyperuricemia on mesenteric arterial tone (main and second order branch) and morphology in experimental CRI. Forty-four Sprague-Dawley rats were 5/6 nephrectomized (NX) or Sham-operated and fed 2.0% oxonic acid or control diet for 9 weeks. Results: Oxonic acid feeding elevated plasma uric acid levels 2.4 and 3.6-fold in the NX and Sham groups, respectively. Plasma creatinine and urea were elevated 2-fold and blood pressure increased by 10 mmHg in NX rats, while hyperuricemia did not significantly influence these variables. Right and left ventricular weight, and atrial and B-type natriuretic peptide mRNA content were increased in NX rats, but were not affected by hyperuricemia. In the mesenteric artery, hyperuricemia did not influence vasoconstrictor responses in vitro to norepinephrine or potassium chloride. The small arteries of NX rats featured hypertrophic remodeling independent of uric acid levels: wall to lumen ratio, wall thickness and cross-sectional area were increased without changes in lumen diameter. In the main branch, vasorelaxations to acetylcholine were impaired in NX rats, but were not affected by hyperuricemia. In contrast, relaxations to the large-conductance Ca 2+ -activated K + -channel (BK Ca ) opener NS-1619 were reduced by oxonic acid feeding, whereas responses to nitroprusside were not affected. Conclusions: Experimental hyperuricemia did not influence cardiac load or vascular remodeling, but impaired BK Ca -mediated vasorelaxation in experimental CRI.

Research paper thumbnail of Direct effect of thyroxine on pig sphincter of Oddi contractility

Digestive diseases and sciences, 2001

Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function... more Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function disturbances (stenosis or dyskinesia) may prevent normal bile flow and thus enhance the probability of common bile duct (CBD) stone formation. Previously we have shown that there is an increased prevalence of diagnosed hypothyroidism in CBD stone patients, compared with gallbladder stone patients or age-, sex-, and hospital-admission-adjusted controls. The present study was done to test the hypothesis that thyroxine directly effects the SO. The specificity of the effects of thyroxine were studied by comparing with triiodothyronine (T3), progesterone, cortisone, estrogen, and testosterone. For ex vivo studies three or four successive 1 to 1.5-mm SO rings were prepared from each pig and placed between two hooks in oxygenated physiologic salt solution at 37 degrees C. SO contraction was measured with isometric force displacement transducers and registered on a polygraph. Each SO ring was s...

Research paper thumbnail of Daily Liquorice Consumption for Two Weeks Increases Augmentation Index and Central Systolic and Diastolic Blood Pressure

PLoS ONE, 2014

Background: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alte... more Background: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively.

Research paper thumbnail of Metabolic Syndrome in IgA Glomerulonephritis

Nephron Extra, 2014

Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney dis... more Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable.

Research paper thumbnail of PO5-125 Cyba C242T Gene Polymorphism and Flow-Mediated Vasodilation in a Population of Young Adults. The Cardiovascular Risk in Young Finns Study

Atherosclerosis Supplements, 2007

Research paper thumbnail of Plasma cell-free DNA levels are elevated in acute Puumala hantavirus infection

Introduction: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome called nep... more Introduction: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome called nephropathia epidemica (NE). The aim of the present study was to evaluate plasma cell-free DNA (cf-DNA) levels and urinary cf-DNA excretion in acute NE as well as their associations with the severity of the disease.

Research paper thumbnail of High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats

American Journal of Hypertension - AMER J HYPERTENS, 1996

The effects of long-term high calcium diet and physical exercise and their combined effects on th... more The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m/day. Calcium supplementation was instituted by increasing the calcium content of the chow from 1.1% to 2.5%. During the 23-week study, calcium supplementation attenuated the rise in blood pressure in both trained and nontrained hypertensive animals, whereas exerise training had no significant effect on blood pressure. The high calcium diet alone was associated with reduced plasma and ventricular tissue contents of atrial natriuretic peptide, both of which were increased by exercise. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Neither increased dietary calcium nor endur...

Research paper thumbnail of Tubular Proteinuria and Glomerular Filtration 6 Years after Puumala Hantavirus-Induced Acute Interstitial Nephritis

Nephron Clinical Practice, 2009

We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blo... more We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. Six years after NE, the prevalence of elevated urinary alpha(1)-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs. 109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/- 9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p = 0.035) than the controls. These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

Research paper thumbnail of The Severity of Acute Puumala Hantavirus Infection Does Not Predict the Long-Term Outcome of Patients

Nephron Clinical Practice, 2010

We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and b... more We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and blood pressure in patients 6 years after acute nephropathia epidemica (NE) compared with seronegative controls. The present aim was to establish whether the long-term outcome is determined by the severity of acute illness. Serial plasma interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), creatinine, C-reactive protein, blood cell count as well as 24-hour urinary protein and overnight α(1)-microglobulin and albumin excretions were measured in 37 patients with acute NE. Human leucocyte antigen (HLA)-B, HLA-DRB1, TNF-α(-308) and IL-6(-174) alleles were also analyzed. After 6 years, GFR, blood pressure and urinary protein excretion were examined. There were no associations between the clinical severity of acute NE or the genetic factors determined and the increased GFR, hypertension or 24-hour urinary protein excretion observed 6 years later. The degree of inflammation during the acute phase was higher in patients who had increased urinary excretion of α(1)-microglobulin 6 years later compared with those with no α(1)-microglobulin excretion. Neither the severity of acute NE nor the host genetic factors determined the predicted renal function, blood pressure or 24-hour urinary protein excretion 6 years later.

Research paper thumbnail of Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

Nephron Experimental Nephrology, 2008

To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits... more To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Creatinine clearance was reduced by 54-61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated.

Research paper thumbnail of Preserved Endothelium-Dependent but Impaired β-Adrenergic Relaxation of the Resistance Vessels in Experimental Renal Failure

Nephron Experimental Nephrology, 2002

Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial ... more Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial elasticity. Only little information is available on the functional effects of uraemia on resistance arteries. Therefore, we studied the influence of renal failure on rat small mesenteric vessels. The responses of arterial rings were investigated in a Mulvany myograph 6 weeks after 5/6 nephrectomy or sham operation. The subtotal nephrectomy resulted in a 1.9-fold elevation of plasma urea nitrogen but was without significant effect on blood pressure. Endothelium-dependent relaxations, largely mediated via arterial K(+) channels, were preserved in the resistance vessels of uraemic rats. Endothelium-independent vasorelaxations, mediated via exogenous nitric oxide and the opening of ATP-sensitive K(+) channels, were also unchanged. However, the responses induced by isoprenaline were slightly reduced, indicating impaired relaxation via beta-adrenoceptors in experimental renal failure.

Research paper thumbnail of More than half of the patients with acute Puumala hantavirus infection have abnormal cardiac findings

Scandinavian Journal of Infectious Diseases, 2009

This study was conducted to determine the frequency, severity and outcome of cardiac findings in ... more This study was conducted to determine the frequency, severity and outcome of cardiac findings in patients with acute Puumala hantavirus-induced nephropathia epidemica (NE). 70 consecutive, hospital-treated patients with serologically confirmed NE were prospectively examined using serial electrocardiograms (ECG), plasma troponin I, tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and echocardiography (ECHO). Examinations were repeated after 3 and 12 months. ECG changes were observed in 57% of patients. Plasma troponin I levels remained normal in all. In six patients, ECHO showed left ventricular contraction abnormalities, and 1 patient had mild pericardial effusion. There were no differences in clinical or standard laboratory findings or in plasma TNF-alpha and IL-6 concentrations between patients with and without ECG or ECHO changes. During the follow-up, all acute-phase changes in ECG and ECHO reverted to normal, which probably reflects their benign nature. We conclude that abnormal cardiac findings are surprisingly common during NE.

Research paper thumbnail of Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study

Scandinavian Journal of Clinical & Laboratory Investigation, 2008

Research paper thumbnail of Analysis of cardiovascular responses to passive head‐up tilt using continuous pulse wave analysis and impedance cardiography

Scandinavian Journal of Clinical & Laboratory Investigation, 2009

To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascula... more To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head-up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol. Thirty-three healthy volunteers (21-51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole-body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head-up tilt, and repeated during the same session and on four separate days. During the head-up tilt, diastolic BP (5.2+/-0.6%), heart rate (27.6+/-1.9%) and vascular resistance (12.5+/-1.7%) increased (all p<0.05), while systolic BP (-3.2+/-0.6%), aortic pulse pressure (-23.3+/-1.4%), augmentation index (-11.6+/-0.7%), aortic reflection time (-7.0+/-1.0%), ejection duration (-21.4+/-0.7%), stroke volume (-26.1+/-1.2%) and cardiac output (-5.0+/-1.5%) decreased (all p<0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = -0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head-up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = -0.445). According to Bland-Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days. Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head-up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

Research paper thumbnail of Treatment of secondary hyperparathyroidism by high calcium diet is associated with enhanced resistance artery relaxation in experimental renal failure

Nephrology Dialysis Transplantation, 2003

Background. Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium die... more Background. Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium diet enhances vasodilatation and reduces blood pressure in experimental hypertension. Oral calcium salts are used as phosphate binders in RF. However, the effect of increased calcium intake on arterial tone in RF is unknown. Methods. We investigated the influence of an 8-week high calcium diet (0.3 vs 3.0%) on resistance artery tone in 5/6 nephrectomized (NTX) rats. Calcium was supplemented as carbonate salt, blood pressure measured by tail-cuff, urine collected in metabolic cages, and samples taken for blood chemistry and parathyroid hormone (PTH). Functional studies of isolated thirdorder branches of the mesenteric artery in vitro were performed using the Mulvany multimyograph. Results. Plasma urea was elevated 1.6-fold and systolic blood pressure by 10 mmHg after NTX, while increased calcium intake was without effect on these variables. Plasma PTH and phosphate were raised following NTX, and suppressed by high calcium diet. Vasorelaxations induced by K þ channel agonists 11,12-epoxyeicosatrienoic acid and levcromakalim were impaired after NTX. Vasorelaxation induced by acetylcholine was also reduced following NTX, and experiments with N G -nitro-L-arginine methyl ester, diclofenac and charybdotoxin þ apamin suggested that the K þ channel-mediated component of endothelium-dependent relaxation was deficient after NTX. Increased calcium intake corrected all impairments of vasodilatation in NTX rats.

Research paper thumbnail of Insulin resistance and the progression of IgA glomerulonephritis

Nephrology Dialysis Transplantation, 2007

Background. IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patient... more Background. IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patients progressing to end-stage renal disease. Hypertension, proteinuria and renal insufficiency are risk factors associated with poor prognosis. The role of insulin resistance is unclear in IgAGN. Methods. From a retrospective cohort of IgAGN patients, a total of 174 patients (104 males) were invited for two visits at the clinic, 11 and 16 years (median times) after IgAGN was diagnosed in renal biopsy. Of all the patients, 63% had been diagnosed at least 10 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the first and second visits, or kidney transplantation or start of dialysis. Plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index and cystatin-C were obtained for analysis from 118 patients. Results. IgAGN was progressive in 19.5% of the patients on the second visit. Insulin level and HOMA-IR of the first visit showed significant association with the progression of IgAGN (P ¼ 0.019 and 0.005, respectively). Conclusions. Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Research paper thumbnail of Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise

Naunyn-Schmiedeberg's Archives of Pharmacology, 1999

... 1990). Mika Kähönen · Xiumin Wu · Valérie B. Schini-Kerth · Outi Ylikotila · Pertti Arvola · ... more ... 1990). Mika Kähönen · Xiumin Wu · Valérie B. Schini-Kerth · Outi Ylikotila · Pertti Arvola · Jari-Petteri Tolvanen · Eeva Moilanen · Ilkka Pörsti Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise ...

Research paper thumbnail of Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart

Naunyn-Schmiedeberg's Archives of Pharmacology, 1993

muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites su... more muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT1 receptor subtype localized on coronary endothelial and smooth muscle cells, as well as on cardiomyocytes.

Research paper thumbnail of Penetration of some compounds through blood-brain and blood-testis barriers in chronically hypertensive rats

Acta Physiologica Scandinavica, 1984

Research paper thumbnail of AT1 Receptor Blockade Improves Vasorelaxation in Experimental Renal Failure

It is not known whether angiotensin II type 1 receptor antagonists can influence the function and... more It is not known whether angiotensin II type 1 receptor antagonists can influence the function and morphology of small arteries in renal failure. We investigated the effect of 8-week losartan therapy (20 mg/kg per day) on isolated mesenteric resistance arteries by wire and pressure myographs in 5/6 nephrectomized rats. Plasma urea nitrogen was elevated 1.6-fold after nephrectomy, and ventricular synthesis

Research paper thumbnail of Effects of oxonic acid-induced hyperuricemia on mesenteric artery tone and cardiac load in experimental renal insufficiency

BMC Nephrology, 2015

Background: Recent studies suggest a causal role for increased plasma uric acid in the progressio... more Background: Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). However, uric acid also functions as an antioxidant with possible beneficial effects. Methods: We investigated the influence of hyperuricemia on mesenteric arterial tone (main and second order branch) and morphology in experimental CRI. Forty-four Sprague-Dawley rats were 5/6 nephrectomized (NX) or Sham-operated and fed 2.0% oxonic acid or control diet for 9 weeks. Results: Oxonic acid feeding elevated plasma uric acid levels 2.4 and 3.6-fold in the NX and Sham groups, respectively. Plasma creatinine and urea were elevated 2-fold and blood pressure increased by 10 mmHg in NX rats, while hyperuricemia did not significantly influence these variables. Right and left ventricular weight, and atrial and B-type natriuretic peptide mRNA content were increased in NX rats, but were not affected by hyperuricemia. In the mesenteric artery, hyperuricemia did not influence vasoconstrictor responses in vitro to norepinephrine or potassium chloride. The small arteries of NX rats featured hypertrophic remodeling independent of uric acid levels: wall to lumen ratio, wall thickness and cross-sectional area were increased without changes in lumen diameter. In the main branch, vasorelaxations to acetylcholine were impaired in NX rats, but were not affected by hyperuricemia. In contrast, relaxations to the large-conductance Ca 2+ -activated K + -channel (BK Ca ) opener NS-1619 were reduced by oxonic acid feeding, whereas responses to nitroprusside were not affected. Conclusions: Experimental hyperuricemia did not influence cardiac load or vascular remodeling, but impaired BK Ca -mediated vasorelaxation in experimental CRI.

Research paper thumbnail of Direct effect of thyroxine on pig sphincter of Oddi contractility

Digestive diseases and sciences, 2001

Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function... more Sphincter of Oddi (SO) motility has an important role in the regulation of bile flow. SO function disturbances (stenosis or dyskinesia) may prevent normal bile flow and thus enhance the probability of common bile duct (CBD) stone formation. Previously we have shown that there is an increased prevalence of diagnosed hypothyroidism in CBD stone patients, compared with gallbladder stone patients or age-, sex-, and hospital-admission-adjusted controls. The present study was done to test the hypothesis that thyroxine directly effects the SO. The specificity of the effects of thyroxine were studied by comparing with triiodothyronine (T3), progesterone, cortisone, estrogen, and testosterone. For ex vivo studies three or four successive 1 to 1.5-mm SO rings were prepared from each pig and placed between two hooks in oxygenated physiologic salt solution at 37 degrees C. SO contraction was measured with isometric force displacement transducers and registered on a polygraph. Each SO ring was s...

Research paper thumbnail of Daily Liquorice Consumption for Two Weeks Increases Augmentation Index and Central Systolic and Diastolic Blood Pressure

PLoS ONE, 2014

Background: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alte... more Background: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively.

Research paper thumbnail of Metabolic Syndrome in IgA Glomerulonephritis

Nephron Extra, 2014

Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney dis... more Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable.

Research paper thumbnail of PO5-125 Cyba C242T Gene Polymorphism and Flow-Mediated Vasodilation in a Population of Young Adults. The Cardiovascular Risk in Young Finns Study

Atherosclerosis Supplements, 2007

Research paper thumbnail of Plasma cell-free DNA levels are elevated in acute Puumala hantavirus infection

Introduction: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome called nep... more Introduction: Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome called nephropathia epidemica (NE). The aim of the present study was to evaluate plasma cell-free DNA (cf-DNA) levels and urinary cf-DNA excretion in acute NE as well as their associations with the severity of the disease.

Research paper thumbnail of High calcium diet reduces blood pressure in exercised and nonexercised hypertensive rats

American Journal of Hypertension - AMER J HYPERTENS, 1996

The effects of long-term high calcium diet and physical exercise and their combined effects on th... more The effects of long-term high calcium diet and physical exercise and their combined effects on the development of hypertension, plasma and tissue atrial natriuretic peptide, and arterial function were studied in spontaneously hypertensive rats with Wistar-Kyoto rats serving as normotensive controls. Hypertensive rats were made to exercise by running on a treadmill up to 900 m/day. Calcium supplementation was instituted by increasing the calcium content of the chow from 1.1% to 2.5%. During the 23-week study, calcium supplementation attenuated the rise in blood pressure in both trained and nontrained hypertensive animals, whereas exerise training had no significant effect on blood pressure. The high calcium diet alone was associated with reduced plasma and ventricular tissue contents of atrial natriuretic peptide, both of which were increased by exercise. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Neither increased dietary calcium nor endur...

Research paper thumbnail of Tubular Proteinuria and Glomerular Filtration 6 Years after Puumala Hantavirus-Induced Acute Interstitial Nephritis

Nephron Clinical Practice, 2009

We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blo... more We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4-7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. Six years after NE, the prevalence of elevated urinary alpha(1)-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 +/- 0.05 vs. 0.14 +/- 0.04 g/day; p = 0.006), GFR (119 +/- 19 vs. 109 +/- 14 ml/min/1.73 m(2); p = 0.016) and mean systolic (123 +/- 11 vs. 117 +/- 9 mm Hg; p = 0.012), nighttime systolic (109 +/- 11 vs. 100 +/- 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 +/- 7 vs. 66 +/- 7 mm Hg; p = 0.035) than the controls. These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

Research paper thumbnail of The Severity of Acute Puumala Hantavirus Infection Does Not Predict the Long-Term Outcome of Patients

Nephron Clinical Practice, 2010

We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and b... more We have found greater urinary protein excretion and higher glomerular filtration rate (GFR) and blood pressure in patients 6 years after acute nephropathia epidemica (NE) compared with seronegative controls. The present aim was to establish whether the long-term outcome is determined by the severity of acute illness. Serial plasma interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), creatinine, C-reactive protein, blood cell count as well as 24-hour urinary protein and overnight α(1)-microglobulin and albumin excretions were measured in 37 patients with acute NE. Human leucocyte antigen (HLA)-B, HLA-DRB1, TNF-α(-308) and IL-6(-174) alleles were also analyzed. After 6 years, GFR, blood pressure and urinary protein excretion were examined. There were no associations between the clinical severity of acute NE or the genetic factors determined and the increased GFR, hypertension or 24-hour urinary protein excretion observed 6 years later. The degree of inflammation during the acute phase was higher in patients who had increased urinary excretion of α(1)-microglobulin 6 years later compared with those with no α(1)-microglobulin excretion. Neither the severity of acute NE nor the host genetic factors determined the predicted renal function, blood pressure or 24-hour urinary protein excretion 6 years later.

Research paper thumbnail of Paricalcitol Treatment and Arterial Tone in Experimental Renal Insufficiency

Nephron Experimental Nephrology, 2008

To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits... more To examine whether treatment of secondary hyperparathyroidism with paricalcitol provides benefits to arteries in uremic rats. 5/6-nephrectomized rats were treated (NX+Pari) or not treated (NX) with paricalcitol (200 ng/kg, thrice weekly) for 12 weeks. Aortic histology and isolated segments of the main and 2nd-order mesenteric arterial branches were studied. Creatinine clearance was reduced by 54-61%, plasma phosphate increased 2.1- to 2.5-fold, and blood pressure by 40 mm Hg in both NX groups. PTH increased 13-fold in NX and 5-fold in NX+Pari rats. Calcification in aortic cross-sections increased from 2.1 to 7.1% after paricalcitol. In the large mesenteric artery, vasoconstriction to noradrenaline was reduced in NX+Pari rats. In the large and small arteries, vasorelaxation to acetylcholine was impaired in NX rats and unaffected by paricalcitol. In the small artery, paricalcitol increased nitric oxide synthase inhibition-resistant relaxation to acetylcholine, and maximal relaxation to levcromakalim. The small arteries of NX rats featured increased wall cross-sectional area, while paricalcitol further increased wall thickness and the wall:lumen ratio. Paricalcitol treatment showed both benefits and harmful effects in uremic rats: in the large artery vasoconstriction was reduced but calcification increased, while in the small artery vasorelaxation via potassium channels was moderately improved but hypertrophic remodeling was aggravated.

Research paper thumbnail of Preserved Endothelium-Dependent but Impaired β-Adrenergic Relaxation of the Resistance Vessels in Experimental Renal Failure

Nephron Experimental Nephrology, 2002

Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial ... more Chronic renal failure is associated with increased cardiovascular morbidity and reduced arterial elasticity. Only little information is available on the functional effects of uraemia on resistance arteries. Therefore, we studied the influence of renal failure on rat small mesenteric vessels. The responses of arterial rings were investigated in a Mulvany myograph 6 weeks after 5/6 nephrectomy or sham operation. The subtotal nephrectomy resulted in a 1.9-fold elevation of plasma urea nitrogen but was without significant effect on blood pressure. Endothelium-dependent relaxations, largely mediated via arterial K(+) channels, were preserved in the resistance vessels of uraemic rats. Endothelium-independent vasorelaxations, mediated via exogenous nitric oxide and the opening of ATP-sensitive K(+) channels, were also unchanged. However, the responses induced by isoprenaline were slightly reduced, indicating impaired relaxation via beta-adrenoceptors in experimental renal failure.

Research paper thumbnail of More than half of the patients with acute Puumala hantavirus infection have abnormal cardiac findings

Scandinavian Journal of Infectious Diseases, 2009

This study was conducted to determine the frequency, severity and outcome of cardiac findings in ... more This study was conducted to determine the frequency, severity and outcome of cardiac findings in patients with acute Puumala hantavirus-induced nephropathia epidemica (NE). 70 consecutive, hospital-treated patients with serologically confirmed NE were prospectively examined using serial electrocardiograms (ECG), plasma troponin I, tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and echocardiography (ECHO). Examinations were repeated after 3 and 12 months. ECG changes were observed in 57% of patients. Plasma troponin I levels remained normal in all. In six patients, ECHO showed left ventricular contraction abnormalities, and 1 patient had mild pericardial effusion. There were no differences in clinical or standard laboratory findings or in plasma TNF-alpha and IL-6 concentrations between patients with and without ECG or ECHO changes. During the follow-up, all acute-phase changes in ECG and ECHO reverted to normal, which probably reflects their benign nature. We conclude that abnormal cardiac findings are surprisingly common during NE.

Research paper thumbnail of Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study

Scandinavian Journal of Clinical & Laboratory Investigation, 2008

Research paper thumbnail of Analysis of cardiovascular responses to passive head‐up tilt using continuous pulse wave analysis and impedance cardiography

Scandinavian Journal of Clinical & Laboratory Investigation, 2009

To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascula... more To non-invasively measure central haemodynamics, arterial stiffness, cardiac function and vascular resistance, with the subject in the supine position and during head-up tilt, in order to examine the haemodynamic changes associated with alterations in the augmentation index, and to investigate repeatability and reproducibility of the measurement protocol. Thirty-three healthy volunteers (21-51 years) were investigated using continuous pulse wave analysis from the radial artery with a tonometric sensor, whole-body impedance cardiography and plethysmographic blood pressure (BP) recordings from the fingers. The measurements were performed with the subject supine and during passive head-up tilt, and repeated during the same session and on four separate days. During the head-up tilt, diastolic BP (5.2+/-0.6%), heart rate (27.6+/-1.9%) and vascular resistance (12.5+/-1.7%) increased (all p<0.05), while systolic BP (-3.2+/-0.6%), aortic pulse pressure (-23.3+/-1.4%), augmentation index (-11.6+/-0.7%), aortic reflection time (-7.0+/-1.0%), ejection duration (-21.4+/-0.7%), stroke volume (-26.1+/-1.2%) and cardiac output (-5.0+/-1.5%) decreased (all p<0.05). Augmentation index at rest correlated with aortic systolic BP (r = 0.423), aortic reflection time (r = -0.647), pulse wave velocity (r = 0.287) and age (r = 0.480). The change in augmentation index during head-up tilt correlated with the change in aortic systolic BP (r = 0.469), aortic pulse pressure (r = 0.606), ejection duration (r = 0.374) and heart rate (r = -0.445). According to Bland-Altman and repeatability index analyses, repeatability and reproducibility of the measurements were good during the same session and on separate days. Combined pulse wave analysis and impedance cardiography with the subject in the supine position and during head-up tilt is a repeatable and reproducible method for comprehensive investigation of the cardiovascular function.

Research paper thumbnail of Treatment of secondary hyperparathyroidism by high calcium diet is associated with enhanced resistance artery relaxation in experimental renal failure

Nephrology Dialysis Transplantation, 2003

Background. Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium die... more Background. Vasorelaxation is impaired in renal failure (RF) and hypertension. A high calcium diet enhances vasodilatation and reduces blood pressure in experimental hypertension. Oral calcium salts are used as phosphate binders in RF. However, the effect of increased calcium intake on arterial tone in RF is unknown. Methods. We investigated the influence of an 8-week high calcium diet (0.3 vs 3.0%) on resistance artery tone in 5/6 nephrectomized (NTX) rats. Calcium was supplemented as carbonate salt, blood pressure measured by tail-cuff, urine collected in metabolic cages, and samples taken for blood chemistry and parathyroid hormone (PTH). Functional studies of isolated thirdorder branches of the mesenteric artery in vitro were performed using the Mulvany multimyograph. Results. Plasma urea was elevated 1.6-fold and systolic blood pressure by 10 mmHg after NTX, while increased calcium intake was without effect on these variables. Plasma PTH and phosphate were raised following NTX, and suppressed by high calcium diet. Vasorelaxations induced by K þ channel agonists 11,12-epoxyeicosatrienoic acid and levcromakalim were impaired after NTX. Vasorelaxation induced by acetylcholine was also reduced following NTX, and experiments with N G -nitro-L-arginine methyl ester, diclofenac and charybdotoxin þ apamin suggested that the K þ channel-mediated component of endothelium-dependent relaxation was deficient after NTX. Increased calcium intake corrected all impairments of vasodilatation in NTX rats.

Research paper thumbnail of Insulin resistance and the progression of IgA glomerulonephritis

Nephrology Dialysis Transplantation, 2007

Background. IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patient... more Background. IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patients progressing to end-stage renal disease. Hypertension, proteinuria and renal insufficiency are risk factors associated with poor prognosis. The role of insulin resistance is unclear in IgAGN. Methods. From a retrospective cohort of IgAGN patients, a total of 174 patients (104 males) were invited for two visits at the clinic, 11 and 16 years (median times) after IgAGN was diagnosed in renal biopsy. Of all the patients, 63% had been diagnosed at least 10 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the first and second visits, or kidney transplantation or start of dialysis. Plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index and cystatin-C were obtained for analysis from 118 patients. Results. IgAGN was progressive in 19.5% of the patients on the second visit. Insulin level and HOMA-IR of the first visit showed significant association with the progression of IgAGN (P ¼ 0.019 and 0.005, respectively). Conclusions. Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Research paper thumbnail of Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise

Naunyn-Schmiedeberg's Archives of Pharmacology, 1999

... 1990). Mika Kähönen · Xiumin Wu · Valérie B. Schini-Kerth · Outi Ylikotila · Pertti Arvola · ... more ... 1990). Mika Kähönen · Xiumin Wu · Valérie B. Schini-Kerth · Outi Ylikotila · Pertti Arvola · Jari-Petteri Tolvanen · Eeva Moilanen · Ilkka Pörsti Interleukin-1β-induced nitric oxide synthesis in aortic rings from normal and hyperinsulinaemic rats: effect of physical exercise ...

Research paper thumbnail of Dual action of angiotensin II on coronary resistance in the isolated perfused rabbit heart

Naunyn-Schmiedeberg's Archives of Pharmacology, 1993

muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites su... more muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT1 receptor subtype localized on coronary endothelial and smooth muscle cells, as well as on cardiomyocytes.