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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL035051-03
Application #
3106748
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1986-12-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Wyss, J M; Mozaffari, M S; St John, P L et al. (1993) Cyclosporine-induced nephrotoxicity in deoxycorticosterone-NaCl treated rats. Int J Exp Pathol 74:615-26
Wyss, J M; Oparil, S; Sripairojthikoon, W (1992) Neuronal control of the kidney: contribution to hypertension. Can J Physiol Pharmacol 70:759-70
Wyss, J M; Van Groen, T (1992) Early breakdown of dendritic bundles in the retrosplenial granular cortex of hypertensive rats: prevention by antihypertensive therapy. Cereb Cortex 2:468-76
Chen, Y F; Naftilan, A J; Oparil, S (1992) Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension 19:456-63
Yang, R H; Jin, H; Wyss, J M et al. (1992) Depressor effect of blocking angiotensin subtype 1 receptors in anterior hypothalamus. Hypertension 19:475-81
Yang, R H; Jin, H; Chen, S J et al. (1992) Blocking hypothalamic AT1 receptors lowers blood pressure in salt-sensitive rats. Hypertension 20:755-62
Fox, J; Guan, S; Hymel, A A et al. (1992) Dietary Na and ACE inhibition effects on renal tissue angiotensin I and II and ACE activity in rats. Am J Physiol 262:F902-9
Chen, Y F; Elton, T S; Oparil, S (1992) Quantitation of hypothalamic atrial natriuretic peptide messenger RNA in hypertensive rats. Hypertension 19:296-300
Wyss, J M; Fisk, G; van Groen, T (1992) Impaired learning and memory in mature spontaneously hypertensive rats. Brain Res 592:135-40
Yang, R; Jin, H; Wyss, J M et al. (1992) Salt supplementation does not alter the pressor effect of blocking atrial natriuretic peptide in nucleus tractus solitarii. Hypertension 20:242-6

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