Objective: To determine the roles of vasopressin, the renin-angiotensin system and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat.
Design: The effects of 12 days' treatment with a non-peptide, orally effective V1 antagonist (OPC-21,268) and captopril, individually or together, were compared in male and female Dahl salt-sensitive rats after 10 days on a high-salt diet.
Methods: OPC-21,268 was given in the food, and captopril was administered with osmotic pumps implanted subcutaneously.
Results: Systolic blood pressure (SBP) reached a higher level in untreated males than in untreated females. V1 blockade in males prevented any further increase in SBP during the first week of treatment, but SBP rose thereafter towards the levels found in the untreated males. In females OPC-21,268 had no effect. In males captopril prevented any further increase in SBP. There was no effect of captopril in females during the first week of treatment, but SBP fell to pretreatment levels during the second week. Combined treatment with OPC-21,268 and captopril in males had a smaller antihypertensive effect than either drug alone. In females combined treatment prevented any further increase in SBP.
Conclusions: These findings suggest that both vasopressin and the renin-angiotensin system contribute to the pathogenesis of Dahl salt-sensitive hypertension, but that other factors, possibly 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. It 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.