This is a proposal to study relationships between the production of thromboxane by the kidney and the level of dietary sodium and potassium, and to define the significance of such relationships in terms of regulation of renal function and blood pressure in normotensive and hypertensive rats. The following specific objectives will be addressed. 1. Characterization of the effects of dietary sodium and potassium on renal thromboxane synthesis in terms of anatomical structures affected, mechanisms, and influence on the expression of relationships between vasoactive hormones and renal prostanoids. We will examine the production of thromboxane by isolated glomeruli, renal cortex tubules, and renal medulla slices as a function of the level of dietary sodium and potassium. This will be complemented by investigation of the effect of the same dietary interventions on the release of thromboxane and other prostanoids from isolated renal structures or perfused kidney during challange with a lipolytic stimulus. 2. Definition of the functional significance of the changes in renal thromboxane which are associated with variations in dietary sodium and potassium. We will study the effects on renal functions of inhibitors of thromboxane synthesis, or thromboxane receptor antagonists, in rats maintained on an increased or decreased intake of sodium or potassium so as to vary renal thromboxane. 3. Investigation of relationships between the opposite effects of dietary sodium and potassium on renal thromboxane and their reciprocal influence on the development of hypertension. We will study the relationships between blood pressure and renal thromboxane production as a function of dietary sodium and potassium in spontaneously hypertensive rats, Dahl's salt-sensitive rats, and DOCA-treated rats. In addition, we will contrast as a function of dietary sodium and potassium the effect of thromboxane synthesis inhibitors and of receptor blockers on blood pressure and renal function in the three aforementioned models of hypertension in rats.
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