Hypertension accounts for one third of end stage renal disease (ESRD) in blacks and ESRD is 4 times more common in the black than in the white population. There is as yet little evidence that the availability of effective antihypertensive therapy has reduced the prevalence of hypertensive nephrosclerosis as a cause of ESRD. We postulate that essential hypertension is secondary to a primary renal disturbance related to derangements in renal function that contributes to an impaired renal capacity to appropriately adjust sodium excretion in a normotensive state. Understanding of this postulated primary renal abnormality is necessary to prevent hypertensive renal disease. The already established Nephrology Research and Training Center at this institution seeks to become a Renal Center to explore, utilizing an interdisciplinary basic and clinical investigative approach, this hypothesis in general and the nature of the renal abnormalities. The interactions among hormones and humoral agents (catecholamines, antidiuretic hormone, aldosterone, prostaglandins, bradykinin, angiotensin II, etc) which may regulate sodium reabsorption in the proximal tubule, ascending limb and cortical collecting tubule will be examined (Project 2, 3, and 8). The intrarenal juxtaglomerular apparatus mechanism to control filtered solute load will be explore utilizing a developmental approach and an isolated in vitro preparation (Project 4). In animal genetic models of essential hypertension and in experimental renal hypertension, renal epithelial intracellular sodium chloride concentrations (electron microprobe), hormonal and endothelial regulation of renal vascular reactivity and ion transport and in vivo tubulo- glomerular feedback sensitivity will be examined before and after the development of hypertension (Projects 5, 6 and 7). In clinical studies, we will determine if hypertensive nephrosclerosis as a cause of ESRD has been reduced over the past decade; a prospective trial of antihypertensive drug therapy in patients with biopsy-proven nephrosclerosis will examine stability of GFR (Project 1). Finally we will investigate the mechanism of cyclosporine-induced increased renal vascular resistance and hypertension as a drug-induced model of essential hypertension in man (Project 9).
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