AJP - Endocrinology and Metabolism, Vol 260, Issue 4 E521-E525, Copyright © 1991 by American Physiological Society

ARTICLES

Effects of endothelin on in vitro renin secretion

O. Moe, A. Tejedor, W. B. Campbell, R. J. Alpern and W. L. Henrich
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.

The ability of endothelin-1 (ET-1) to directly inhibit renal renin secretion in the presence of a renin stimulator is unknown, as is the mechanism of action of any renin inhibition. Thus direct effects of ET-1 on renin secretion were investigated in two distinct preparations: rat kidney cortical slices and isolated juxtaglomerular cells (JGC). In rat kidney cortical slices, ET-1 reduced basal renin release by 20 (P less than 0.05) and 44% (P less than 0.005) at 10(-9) and 10(-8) M, respectively. To test the efficacy of ET-1 as a renin inhibitor, experiments were performed in the presence of the renin stimulator isoproterenol (10(-5) M). Addition of isoproterenol to cortical slices increased renin release by 97% (P less than 0.001); ET-1 (10(-8) M) limited this increase in renin release by isoproterenol by 80% (P less than 0.05). Similar effects were observed in JGC as ET-1 (10(-8) M) significantly reduced basal renin secretion by 26% (P less than 0.05). In isolated JGC, isoproterenol increased renin secretion by 151% (P less than 0.001); ET-1 (10(-8) M) significantly reduced this stimulated increase in renin secretion by 68%. The mechanism of renin inhibition was examined by testing the effects of the intracellular calcium buffer 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10(-6) M) in JGC. BAPTA alone increased renin secretion in JGC by 116% (P less than 0.01); when the combination of (10(-6) M) BAPTA and ET-1 (10(-8) M) were tested in the JGC, renin secretion still increased significantly (by 78%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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