ATTENUATION OF GENETIC-HYPERTENSION AFTER SHORT-TERM VASOPRESSIN V1A RECEPTOR ANTAGONISM

Abnormalities of the vasopressin system are found in genetic hypertens ion. This study compares the delayed effects of a brief period of vaso pressin V1A receptor blockade and angiotensin-converting enzyme inhibi tion in young female and male spontaneously hypertensive rats (SHR) on the development of hypertension in adult life. In a separate study, t he role of vasopressin in the maintenance of blood pressure in adult S HR was assessed Young SHR received either the nonpeptide vasopressin V IA receptor antagonist OPC-21268, the angiotensin-converting enzyme in hibitor ramipril, or vehicle from 6 to 10 weeks of age. During the tre atment 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 +/-1 mm Hg in OPC-21268-treated, and 200+/-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 co mpared with male SHR. The sustained attenuation in blood pressure was not associated with significant cardiovascular structural changes (lef t ventricular-to-body weight ratio, renal weight-to-body weight ratio, mesenteric resistance artery media-to-lumen ratio). Results of vasopr essin V1A receptor binding kinetics and plasma renin or aldosterone co ncentrations did not suggest a lasting effect of OPC-21268 on the vaso pressin system or of ramipril on the renin-angiotensin system followin g treatment withdrawal. One week of OPC-21268 treatment in adult SHR h ad no effect on systolic blood pressure, indicating that vasopressin i s not involved in the maintenance of blood pressure. In contrast, this study demonstrates the novel finding that brief vasopressin V1A block ade in young SHR attenuates the development of hypertension in adult S HR despite withdrawal of drug treatment. These results support a role for vasopressin in the development of hypertension.