ROLE OF VASOPRESSIN, THE RENIN-ANGIOTENSIN SYSTEM AND SEX IN DAHL SALT-SENSITIVE HYPERTENSION

Objective: To determine the roles of vasopressin, the renin-angiotensi n system and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat. Design: The effects of 12 days' treatment with a non-pe ptide, orally effective V1 antagonist (OPC-21 268) and captopril, indi vidually or together, were compared in male and female Dahl salt-sensi tive rats after 10 days on a high-salt diet. Methods: OPC-21 268 was g iven in the food, and captopril was administered with osmotic pumps im planted subcutaneously. Results: Systolic blood pressure (SBP) reached a higher level in untreated males than in untreated females. V1 block ade in males prevented any further increase in SBP during the first we ek of treatment, but SBP rose thereafter towards the levels found in t he untreated males. In females OPC-21 268 had no effect. In males capt opril prevented any further increase in SBP. There was no effect of ca ptopril in females during the first week of treatment, but SBP fell to pretreatment levels during the second week. Combined treatment with O PC-21 268 and captopril in males had a smaller antihypertensive effect than either drug alone. In females combined treatment prevented any f urther increase in SBP. Conclusions: These findings suggest that both vasopressin and the renin-angiotensin system contribute to the pathoge nesis of Dahl salt-sensitive hypertension, but that other factors, pos sibly including the sympathetic nervous system, are also involved. Sex also affects the severity of this form of hypertension and influences the relative roles of vasopressin and the renin-angiotensin system. I t is likely that the gonadal steroid hormones modulate the activity of the pathogenetic factors in this form of hypertension at a central or peripheral level.