Studies of the pathogenesis of essential hypertension indicate that genetic abnormalities, associated with the pathology of hypertensive states, may express themselves as defects in kidney's ability to excrete sodium (Na) adequately. The mechanisms involved in this renal defect are not clearly understood and may include defective membrane ion transport systems. Patients with essential hypertension have been shown to exhibit defective red cell membrane Na-Li exchange, and recent evidence indicates that this exchange system is similar to the Na-H exchange system in the mammalian renal proximal tubular brush border membranes. Since most of the filtered Na is reabsorbed in the proximal tubules, it seemed reasonable that defects in proximal tubular sodium transport systems may be involved in the renal defect in Na elimination associated with the pathogesis of hypertension. This proposal is designed to examine the hypothesis that the abnormalities in Na elimination by the kidney in hypertension may be due to defects in one or more modes of Na entry across the luminal membranes and the basolateral membranes of renal proximal tubular cells. Specifically, this project will examine whether membrane Na transport mechanisms responsible for Na absorption in the proximal tubules, i.e., 1) Na-H exchange, 2) Na diffusion, 3) brush border membrane Na-D-glucose and Na-PO4 co-transports, and 4) basolateral membrane Na+/K+-ATPase-mediated transport are associated with the pathogenesis of hypertension. This will be accomplished first by studying the membrane Na transport mechanisms in the kidney proximal tubules of hypertensive rats and those of rats at the various stages in the development of hypertension. Additional studies will then be carried out to determine the effects of antihypertensive drug therapy and dietary Na on the Na transport mechanisms in the hypertensive rat models. Thus, at its conclusion this project will demonstrate whether membrane Na transport mechanisms within the kidney are associated with the pathogenesis of hypertension, and whether drug therapy and dietary Na intake affect them. As a part of the five (5) year Minority School Faculty Development plan, this research project will expand the knowledge base and the technical expertise of the principal investigator, leading him to a productive career in the hypertension research.