Abstract

This research concerns the coupling role played by calcium in the secretion of renin from the kidney. Rat renal cortical slices are used. Transmembrane Na gradient, via operation of a putative Na-Ca exchange mechanism, affects intracellular Ca (Cai). Na gradient is reduced by increases in Nai (achieved by inhibition of Na, K-ATPase using low Ke, ouaban or vanadate) or decreases in effects on renin secretion. Na gradient is increased by decreasing Nai (by stimulating Na, K-ATPase using phenytoin, isoproterenol). Phenytoin and isoproterenol stimulate secretion and this can be blocked by agents which increase Cai Depolarization of the membrane (with high K) inhibits secretion in a Ca-dependent manner; the effect is blocked by D-600, a specific Ca-antagonist. Other Ca-antagonists are being studied, and their interaction with Cae. Peptides such as angiotensin II and antidiuretic hormone inhibit secretion in a Ca-dependent manner. The possibility that they act by depolarization, is being assessed by trying to block the effects with Ca-antagonists. The findings fit the hypothesis that Ca plays an inhibitory coupling role in renin secretion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024880-08
Application #
3337862
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1979-12-01
Project End
1988-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

Jones-Dombi, T; Churchill, P (1993) BAY K 8644 inhibits renin secretion in isolated perfused rat kidneys. Life Sci 53:1531-7
Churchill, P C; Ellis, V R (1993) Pharmacological characterization of the renovascular P2 purinergic receptors. J Pharmacol Exp Ther 265:334-8
Churchill, P C; Ellis, V R (1993) Purinergic P2y receptors stimulate renin secretion by rat renal cortical slices. J Pharmacol Exp Ther 266:160-3
Jones-Dombi, T; Churchill, P (1993) The baroreceptor mechanism for controlling renin secretion: effect of calcium channel blockers. J Pharmacol Exp Ther 266:274-8
O'Leary, D S; Rossi, N F; Churchill, P C (1993) Muscle metaboreflex control of vasopressin and renin release. Am J Physiol 264:H1422-7
Churchill, M C; Churchill, P C; Bidani, A K (1993) The effects of cyclosporine in Lewis rats with native and transplanted kidneys. Transplantation 55:1256-60
Griffin, K A; Bidani, A K; Ouyang, J et al. (1993) Role of endothelium-derived nitric oxide in hemodynamic adaptations after graded renal mass reduction. Am J Physiol 264:R1254-9
Churchill, P; Churchill, M; Bidani, A et al. (1993) Streptozotocin-induced renal hemodynamic changes in isogenic Lewis rats: a kidney transplant study. Am J Physiol 264:F100-5
Churchill, P C; Ellis, V R (1992) Dantrolene stimulates renin secretion by rat renal cortical slices but fails to block calcium-dependent inhibition. Life Sci 51:853-8
Churchill, P C; Churchill, M C; Bidani, A K (1992) Kidney cross transplants in Dahl salt-sensitive and salt-resistant rats. Am J Physiol 262:H1809-17

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