Evidence against a pressor role for vasopressin in spontaneous hypertension.

Abstract

Received May 12, 1986; accepted October 6, 1986. to WKY, 1 ' 2 and at 5 and 8 weeks of age VP release is exaggerated in SHR relative to WKY in response to a decrease in plasma volume in vivo 3 or following exposure of the hypothalamoneurohypophyseal system to acetylcholine and angiotensin II in vitro. 4 ' 5 Thus, increased secretion of VP in response to selected stimuli may underlie the elevation of plasma and urinary VP in SHR.Peripheral resistance is elevated in SHR, 6 ' 7 and this elevation is thought to be central to the hypertensive process. Although increased activity of the sympathetic nervous system in SHR' represents one mechanism contributing to the elevated peripheral resistance, VP may also contribute to the elevation of peripheral resistance in this model of hypertension. In addition to the elevations in circulating VP already mentioned, the pressor potency of VP is greater in SHR than in WKY.9 -I0 The pressor potency of VP in SHR appears to stem from impairment of the baroreceptor reflexes that buffer against the pressor effects of VP in WKY.10 '" These observations, in conjunction with the

Effects of the Nonpeptide V 1 Vasopressin Receptor Antagonist SR49059 in Hypertensive Patients

“…This pure V 1 R vascular antagonist profile is of importance when one considers the "ideal" profile of a AVP antagonist to be developed as an antihypertensive agent. Based on the elegant studies performed by Sladek et al 7,33 with peptide antagonists in the spontaneously hypertensive rat, a pure V 1 R antagonist is not expected to produce a sustained decrease in blood pressure, whereas a mixed V 1 /V 2 R antagonist will achieve a reduction in blood pressure via alterations of both peripheral resistances and circulating blood volume. However, the effective and safe ratio of V 1 /V 2 R antagonism remains to be established because of the study by Hofbauer et al, 34 who observed in DOCA-salt hypertensive rats that the administration of a mixed V 1 /V 2 R peptide antagonist led to a greater blood pressure reduction than a pure V 1 R antagonist although at the expense of water loss and hypernatremia.…”

Attenuation of spontaneous hypertension in rats by a vasopressin antagonist.

“…A role for VP in spontaneous hypertension was supported by early studies in which injection of a VP antiserum lowered blood pressure in strokeprone SHR, 8 but studies employing short-term administration 3 or long-term infusion of a specific antagonist of the vascular effects of VP, d(CH2) 3 Tyr(Me)arginine vasopressin (AVP), 9 suggested that the vasoconstrictor action of VP was not an important component of the hypertension in SHR. Shortterm administration of the antagonist to 11-weekold SHR resulted in a small decrease in mean arterial pressure (9 ± 1 mm Hg), 3 but long-term infusion of the antagonist from 4 to 12 weeks of age at rates that blocked the pressor actions of VP did not alter the course of systolic hypertension.…”

“…Shortterm administration of the antagonist to 11-weekold SHR resulted in a small decrease in mean arterial pressure (9 ± 1 mm Hg), 3 but long-term infusion of the antagonist from 4 to 12 weeks of age at rates that blocked the pressor actions of VP did not alter the course of systolic hypertension. 9 This vascular antagonist has weak antidiuretic agonist properties (0.3 vs 323 U/mg for VP). Thus, the failure to obtain antihypertensive effects with this antagonist comparable to those reported with VP antiserum could have reflected the opposite action of the VP analogue and the VP antiserum on the renal action of VP.…”

Contribution of Endogenous Vasopressin to Regional Hemodynamics in Borderline-Hypertensive Hiroshima Rats

“…Some studies have concluded that vasopressin is not a vital hormone for the onset and maintenance of hypertension in SHR (19,20). Okada et al (9) reported that the V1A is rarely effective in lowering AP in intact SHR.…”

“…3, the plasma concentration of AVP was significantly greater in BHR than in NCR (n 5 each, p 0.05) at baseline, and it was significantly increased by ganglionic blockade (AVPBHR 1.60 0. 20 …”