Contribution of Endogenous Vasopressin to Regional Hemodynamics in Borderline-Hypertensive Hiroshima Rats (original) (raw)
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Attenuation of spontaneous hypertension in rats by a vasopressin antagonist
Hypertension, 1988
Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH 2 ) 3 -Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V,) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CHi) r D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension hi SHR (p < 0.05) without altering Mood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 fig/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p < 0.007). Resting mean arterial pressure measured by Indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 ± 4 vs 157 ± 4 mm Hg;p < 0.05). Heart rate also was significantly reduced by the drug (351 ± 6 vs 392 ± 7 beats/ min; p < 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age. All of these parameters returned to the levels observed hi untreated SHR within 2 weeks after drug withdrawal. Although this antagonist has both V, and V 2 (antidiuretlc) antagonist properties, the infusion protocol used hi this study resulted in antagonism of the pressor action of vasopressin but incomplete antagonism of the antldluretk action of vasopressin. Thus, the mechanism responsible for the antihypertensive action of this antagonist is not clear, but the results suggest that long-term blockade of the actions of endogenous vasopressin does alter the course of hypertension hi SHR. KEY WORDS • vasopressin • spontaneously hypertensive rats • vasopressin antagonist blood pressure • vascular resistance P ERIPHERAL resistance is elevated in spontaneously hypertensive rats (SHR), 12 and this elevation is thought to be central to the hypertensive process. Evidence of elevated plasma and urinary vasopressin (VP) in SHR, 3 -4 and the findings that the VP response to a decrease in plasma volume in vivo 5 or following exposure of the hypothalamo-neurohypophyseal system to acetylcholine and angiotensin II in vitro 6 -7 is exaggerated in 5-and 8-week-old SHR, led to the hypothesis From the
Impaired control of vasopressin release in hypertensive subjects with cardiac hypertrophy
…, 1987
The effects of graded lower body negative pressure (-10 and-40 mm Hg) on vascular resistance and plasma vasopressin, norepinephrine, and renin activity were assessed in seven hypertensive subjects with left ventricular hypertrophy and seven sex-matched and age-matched normotensive subjects. In both groups increasing levels of lower body negative pressure induced a progressive decrease in right atrial pressure and an increase in vascular resistance. In normal subjects plasma vasopressin, norepinephrine, and renin activity were progressively raised, whereas only the higher level of stimulation increased plasma renin activity, norepinephrine, and vasopressin in hypertensive subjects. Propranolol induced a significant increase in plasma vasopressin in normal subjects (from 1.3 ± 0.1 to 2.0 ± 0.1 pg/ml; p<0.05) but not in hypertensive subjects. In this latter condition-10 mm Hg lower body negative pressure failed to increase plasma vasopressin, norepinephrine, and renin activity in normal subjects. Propranolol abolished the change in plasma renin activity in both groups, reduced the increase in vascular resistance induced by-40 mm Hg lower body negative pressure in normotensive subjects, but did not modify the rise in vasopressin elicited by this stimulus in normal subjects or the humoral and hemodynamic reflex responses evoked in hypertensive subjects. These results suggest that cardiopulmonary receptors are involved in the control of vasopressin release in normal subjects, whereas in hypertensive subjects with left ventricular hypertrophy, this control is altered because of an impaired function of cardiopulmonary receptors. (Hypertension 10: 595-602, 1987) KEY WORDS • propranolol • lower body negative pressure • norepinephrine A LTHOUGH the sensitivity of the nonosmotic / \ control of arginine vasopressin (AVP) release A. JL. in humans seems to be somewhat controversial, 1 " 4 recent reports 5 ' 6 support the hypothesis that factors other than blood osmolarity are involved in the regulation of AVP release in humans. In particular, Leimbach et al. 5 demonstrated that combined unloading of cardiac and arterial baroreceptors induced by lower body negative pressure (LBNP) increases plasma AVP in subjects with high plasma osmolality. Egan et al. 6 reported that the selective unloading of cardiopulmonary receptors, by thigh-cuff inflation, increases plasma AVP levels in humans. These observations raise the possibility that AVP release may be altered in patients with impaired cardiopulmonary or arterial baroreceptor reflex responsiveness.
The Role of Vasopressin in Essential Hypertension
Amer J Hypertens, 1997
To study the role of vasopressin (VP) in essential hypertension, we examined plasma levels of VP and blood pressure (BP) response to an orally active V 1 receptor antagonist, OPC-21268, in hypertensive patients on diets with different sodium contents. Plasma VP was determined in 12 normotensive subjects and 12 patients with mild essential hypertension on a regular sodium diet, and in eight hypertensive patients on a high sodium (250 mmol/day) and a low sodium (25 mmol/day) diet. BP response was examined for 4 h after single oral administration of OPC-21268 (100 mg) or placebo in eight patients on the regular diet, and in six patients on the high and low sodium diets. In four patients on the regular diet, the effects of OPC-21268 on the baroreflex control of heart rate were also examined with intravenous injections of methoxamine. Plasma VP did not differ between the normotensive and hypertensive subjects. Levels of VP in the plasma was higher in the high sodium than in the low sodium period, but the difference was not significant. BP and heart rate did not change significantly after administration of OPC-21268 or placebo under either condition. OPC-21268 also failed to lower BP in salt-sensitive patients on the high sodium diet. The baroreceptor reflex sensitivity was not modified by the administration of OPC-21268. Our results suggest that VP does not play an important role in mild essential hypertension through its action on the V 1 receptors regardless of dietary sodium intake. Am
Cardiovascular actions of vasopressin at the ventrolateral medulla
Hypertension, 1990
Vasopressin acts at a number of sites in the central nervous system to alter arterial pressure. This study investigated the hypothesis that vasopressin acts at the rostral ventrolateral medulla to increase arterial pressure. The rostral pressor area of the medulla oblongata was exposed in urethane-anesthetized rats prepared for topical application of vasopressin. A 3-minute application of vasopressin (range 10"* to 10" 3 M) produced dose-dependent increases in arterial pressure that averaged between 2±1 and 65±11 mm Hg (p<0.01). Tachycardia was not a consistent response at any concentration of vasopressin. Intravenous administration of a V, vasopressin antagonist did not modify the pressor response produced by topical application of vasopressin (10 M). Application of the Vi antagonist to the rostral pressor area, however, prevented the production of a pressor effect to subsequent topical application of vasopressin (10~4 M). These experiments suggest that vasopressin stimulates the activity of vasomotor neurons in the rostral ventrolateral medulla by a mechanism that involves a neuronal V, receptor.
Role of vasopressin in essential hypertension
Journal of Hypertension, 1997
Background Arginine vasopressin (AVP), in addition to being an antidiuretic hormone, might also have pressor effects relevant to the maintenance of hypertension. Results from several experimental and clinical studies suggested that the pressor function of AVP is more important in low-renin hypertension and in the saltloaded state and that it might be further maximized under sympathetic suppression. Objective To assess whether selective vasopressin receptor inhibition lowers the blood pressure in a racially diverse group of low-renin hypertensive subjects. Methods Thirty-nine hypertensive subjects (16 Caucasian, 23 African-American) eating a 200 mmol/day sodium diet were administered a single intravenous dose of a selective vasopressin receptor antagonist and their blood pressure was monitored constantly for the ensuing 3 h. The protocol was repeated 3 days later after treatment with a single oral dose of 0.4 mg clonidine. Results Of these patients, 54% had their blood sampled for determination of hormone profiles. African-Americans with hypertension had higher baseline plasma AVP levels than did Caucasians (1.13 ± 0.05 versus 0.37 ± 0.06 pg/ml, respectively, P < 0.05), and lower plasma renin activity (0.34 ± 0.07 versus 1.03 ± 0.08 ng/ml per h, respectively, P < 0.05). Selective vasopressin receptor inhibition lowered the mean arterial pressure in African-Americans but not that in Caucasians (lowering by 28 ± 4 mmHg in African-Americans versus lowering by 5 ± 3 mmHg in Caucasians, P < 0.05). Moreover, vasopressin receptor blockade further reduced the arterial pressure in African-Americans but not that in Caucasians after pretreatment with clonidine. Conclusion AVP seems to play a more important role as a pressor hormone in maintaining the elevation of arterial pressure in African-American hypertensives than it does in Caucasian hypertensives.
Brain Research, 1988
In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (l) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4-12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200/~g at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5-11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs (P < 0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs (P < 0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR. In contrast, the suppression of renal renin concentration previously observed in SHRs was abolished when the hypertension was prevented by 6-OHDA treatment suggesting that the reduced renin concentration in mature SHR is a secondary response to the hypertension.
Arginine vasopressin modulates the central action of angiotensin II in the dog
Hypertension, 1983
Endogenous vasopressin may interact with central autonomic nervous system factors in the regulation of cardiovascular function. In 25 morphine/chloralose-anesthetized dogs, we studied the magnitude of the pressor response produced by an infusion of angiotensin II (All) into the vertebral arteries (VA), before and after intracisternal (n = 10), intravertebral (n = 9), or intravenous (n = 6) administration of a competitive antagonist of arginine vasopressin (AVP) [d(CH 2)5iyr(Me) AVP]. The dose response curve to vertebral artery infusion of AH (range 2-20 ng/ kg/mih) was significantly (p < 0.05) shifted to the right of control after injection of the AVP antagonist (10 Mg/kg) into the cisterna magna; the ED at 20 mm Hg being almost double after central AVP blockade. This effect of AVP blockade was confined only to the cardiovascular response mediated by All via the vertebral arteries. When pressor doses of All were injected into either a vein (i.v.) or the cisterna magna of these same dogs, the increases in mean blood pressure were the same before and after AVP antagonist treatment. In another group of anesthetized dogs, we investigated whether the reduced reactivity to intravertebral All could be duplicated by giving the AVP antagonist either via the vertebral artery or i.v. Only the cisterna magna route was effective in causing a blunting of the pressor response to vertebral artery AH. These data demonstrate a previously unknown interaction between vasopressin and the centrally mediated pressor response to intravertebral AH. (Hypertension 5 (supp V): V-94-V-100, 1983) KEY WORDS • blood pressure • angiotensin II • vasopressin • neuropeptides area postrema • central autonomic function • baroreceptor reflexes • neuroendocrine mechanisms I T is well established that in the dog the area postrema of the fourth ventricle has a role in the neural control of cardiovascular function by acting, in part, to enhance central vasomotor sympathetic activity in response to increased blood levels of angiotensin II (All). 1 " 5 In addition, recent data suggest that the effects of AH at the dog's area postrema may depend upon the activity of endogenous brain peptides such as the opioid system. 6 Other studies have indicated that there are reciprocal direct connections between the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus and the nucleus tractus solitarii (NTS) in the brain stem. 7 8 Long descending projections from PVN to the dorsal motor nuclei of the vagus nerve (DMV), the NTS and upper spinal cord have
Osmotic regulation of vasopressin and renin in spontaneously hypertensive rats
Hypertension, 1987
Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p< 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H 2 O; p<0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY. Vasopressin release was significantly increased in response to an increase in osmolality of 12 mosm/kg H 2 O in all groups (p<0.01), but the response was not significantly different in explants of SHR and WKY at any age. The comparable response of the vasopressin system to osmotic challenge in SHR and WKY is in contrast to the previously observed hyperresponsiveness of the vasopressin system to an acute decrease in plasma volume and to acetylcholine in vitro. Thus, it indicates that the previously observed hyperresponsiveness of the vasopressin system is specific to the stimulus rather than a generalized phenomenon. (Hypertension 10: 476-483, 1987) KEY WORDS • hypertension • renin-angiotensin system • renal renin content A LTERATIONS in the responsiveness of the /\ vasopressin (VP) and renin systems to an A. \. acute decrease in plasma volume have been observed in spontaneously hypertensive rats (SHR). Specifically, during the development of hypertension in SHR the VP response to an acute decrease in plasma volume is exaggerated, but the renin response is suppressed when compared with that in age-matched nor-From the motensive Wistar-Kyoto rats (WKY). 1 The present studies were performed to evaluate whether the VP and renin systems show altered responsiveness to extracellular fluid osmolality and sodium concentration, respectively. VP release is stimulated by increased plasma osmolality detected by hypothalamic osmoreceptors, 2 ' 3 while renin release is suppressed by elevated plasma sodium due to direct renal effects 4 and, possibly, as a central nervous system-mediated response to changes in cerebrospinal fluid (CSF) sodium concentration. 5 Enhanced VP sensitivity to increases in osmolality have been observed in sheep with deoxycorticosterone acetate (DOCA)-induced hypertension, 6 and a correlation between elevated sodium intake and elevated plasma VP exist in hypertensive men, but not normotensive men, over 50 years of age. 7 In contrast, the increase in CSF VP elicited by intraventricular perfusion with hypertonic saline was re-