Attenuation of genetic hypertension after short-term vasopressin V1A receptor antagonism

Abnormalities of the vasopressin system are found in genetic hypertension. This study compares the delayed effects of a brief period of vasopressin V1A receptor blockade and angiotensin- converting enzyme inhibition in young female and male spontaneously hypertensive rats (SHR) on the development of hypertension in adult life. In a separate study, the role of vasopressin in the maintenance of blood pressure in adult SHR was assessed. Young SHR received either the nonpeptide vasopressin V1A receptor antagonist OPC-21268, the angiotensin-converting enzyme inhibitor ramipril, or vehicle from 6 to 10 weeks of age. During the treatment period, OPC-21268 and ramipril reduced systolic blood pressure compared with control SHR (P<.001). Blood pressure in male SHR 7 weeks after treatment withdrawal was 178 ±1 mm Hg in ramipril-treated, 184 ±2 mm Hg in control SHR (P<.001). Similar results were seen in female SHR, although both OPC-21268 and ramipril were less effective antihypertensive agents in female compared with male SHR. The sustained attenuation in blood pressure was not associated with significant cardiovascular structural changes (left ventricular- to-body weight ratio, renal weight-to-body weight ratio, mesenteric resistance artery media-to-lumen ratio). Results of vasopressin VIA receptor binding kinetics and plasma renin or aldosterone concentrations did not suggest a lasting effect of OPC-21268 on the vasopressin system or of ramipril on thee renin-angiotensin system following treatment withdrawal. One week of OPC-21268 treatment in adult SHR had no effect on systolic blood pressure, indicating that vasopressin is not involved in the maintenance of blood pressure. In contrast, this study demonstrates the novel finding that brief vasopressin V1A blockade in young SHR attenuates the development of hypertension in adult SHR despite withdrawal of drug treatment. These results support a role for vasopressin in the development of hypertension.