The overall scientific objective of the program project is to determine the mechanisms by which neurohumoral factors participate in the genesis and maintenance of hypertension in a variety of animal models and in man. The seven projects deal at a cellular level with the regulation of neuronal function (projects 1-3 and 6) and tubulo-glomerular function (projects 4 and 5); at an integrative level with the regulation of fluid volumes, peripheral vascular resistance and renal functions (all projects), and at a clinical level with the role of the renin-angiotensin system and the renal nerves in mediating post renal transplant and cyclosporine induced hypertension (projects 2 and 7). Four of the projects are directed at the determination of the contribution of the nervous system to hypertension. Projects 1 and 3 will clarify the hypertension-inducing mechanisms of the central monoaminergic and vasopressinergic systems, respectively. Projects 2 and 6 will investigate the role of the renal nerves in various forms of hypertension. These projects include studies of the selective influence of afferent and efferent renal nerves on the pathogenesis of hypertension and an exploration of the role of adenosine as the chemoreceptor stimulant of renal afferent nerves. The contribution of the sympathetic nervous system to hypertension will be clarified by the results of Projects 1, 2 and 3. These studies will use hypertensive rat models. Project 2 also will investigate the role of the renal nerves in post-renal transplant hypertension in humans, the disease which is the primary focus of the clinical studies which comprise Project 7. The latter will provide an indepth clinical analysis of the factors which contribute to this disease. Projects 4 and 5 will directly investigate the mechanisms by which humoral factors regulate renal hemodynamic and excretory function and thereby induce hypertension. Specifically, Project 4 focuses on the effects of the prostaglandins and the renin-angiotensin system on sodium and fluid reabsorption, while the studies in Project 5 will characterize the angiotensin induced changes in single nephron function which contribute to renovascular hypertension. These seven projects form a well integrated body of clinical and experimental studies which will employ a wide range of modern biological research methods to attack the central goal.