It is our long-term goal to develop an understanding of the role of humoral factors, particularly vasopressin (VP), in the pathogenesis of hypertension. Our recent finding that deoxycorticosterone (DOC)-salt hypertension develops much more slowly in male than in female rats was, then, of particular interest to us since DOC- salt hypertension is dependent upon VP and since pressor responsiveness to VP is higher in male rats than in female rats in most phases of the estrous cycle. In this application, we propose to explore the hemodynamic, humoral, and renal mechanisms underlying the sexual dimorphism of DOC-salt hypertension in the rat as follows. 1) We shall characterize the hemodynamic and humoral differences between male and female rats in the development of DOC-salt hypertension. 2) We shall determine the role of the gonadal steroid hormones in the sexual dimorphism of DOC-salt hypertension. 3) We shall determine the role of the kidney in the sexual dimorphism of DOC-salt hypertension. 4) We shall determine whether there is a sexual dimorphism in DOC-salt hypertension when DOC is given centrally. 5) We shall determine whether sexual dimorphism occurs in other, non-genetic experimental models of hypertension, e.g., two-kidney one-clip hypertension and partial nephrectomy-salt hypertension. This research is relevant to the well known observation that the incidence of hypertension is lower in pre-menopausal women than in men.
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