Chronic and selective vasopressin blockade in spontaneously hypertensive rats

Abstract

Chronic effects of orally available, nonpeptide vasopressin V1 and V2 receptor antagonists on conscious spontaneously hypertensive rats (SHR) were investigated. SHR and Wistar rats were divided into four groups, groups S-1 to S-4 and W-1 to W-4, respectively. Groups S-1 and W-1 were untreated as control. Groups S-2 and W-2 were treated with V1 antagonist, groups S-3 and W-3 received V2 antagonist, and groups S-4 and W-4 were treated with both of V1 and V2 antagonists. V1 and/or V2 antagonists did not affect degree of blood pressure of W-2, W-3, and W-4 rats, and V1 antagonist, alone or combined with V2 antagonist, slightly reduced increases in blood pressure of S-2 and S-4 rats without significance. However, V2 antagonist induced significantly massive and hyposmolar urine in W-3 rats compared with that in S-3 rats. In conclusion, in SHR, circulating vasopressin contributes to increases in blood pressure via either V1 or V2 receptors less than expected from previous studies with antibodies or peptide antagonists.

Evidence for the Involvement of Vasopressin in the Pathophysiology of Adriamycin-induced Nephropathy in Rats

“…Urinary protein excretion of each group proved to be almost the same at weeks 0 and 2. The doses of the drugs were chosen according to the results of a pilot study with Wistar rats, in which these doses of vasopressin antagonists produced reasonable plasma concentrations without disturbing the health of rats [19], Body weight, systolic blood pressure (measured by the tail cuff method), and 24-hour urinary vol ume and urinary protein were measured before and every 2 weeks during the study. At week 10, all rats were sacrificed by decapitation without anesthesia.…”

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

“…3,4,6 AVP implication in the development or maintenance of hypertension, or both, was based on measurements of plasma and urinary AVP levels and responses to specific AVP antisera, peptide or nonpeptide antagonists. [7][8][9] For instance, a recent study demonstrated that in young spontaneously hypertensive rats, the nonpeptide V 1 R antagonist OPC-21268 attenuated the development of hypertension in adult animals. 10 Several potent and selective AVP receptor peptide antagonists have been developed since the original synthesis by Manning and Sawyer of the first potent and selective V 1 receptor antagonist, d(CH 2 ) 5 Tyr(Me)AVP.…”

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

“…Okada et al (9) reported that the V1A is rarely effective in lowering AP in intact SHR. Iriuchijima has already reported that pressor amounts of endogenous vasopressin are secreted only after inhibition of sympathetic activity in DOCA-salt rats (21), but can be secreted in SHR (22) after acute spinal transection or sinoaortic denervation.…”

“…We have recently demonstrated that borderline-hypertensive Hiroshima rats (BHR) are a useful model for investigating the phenotypic traits of hypertension (1). BHR are characterized some investigators have reported that a V1 receptor antagonist (V1A) was not very effective in lowering arterial pressure in intact SHR (9). Thus, it is uncertain whether the vasoconstrictive effect of endogenous vasopressin is enhanced in hypertensive animals under conditions in which the sympathetic vasoconstrictor tone is intact.…”