Effects of endothelin on in vitro renin secretion

O. Moe, A. Tejedor, W. B. Campbell, R. J. Alpern, W. L. Henrich

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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 < 0.05) and 44% (P < 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 < 0.001); ET-1 (10-8 M) limited this increase in renin release by isoproterenol by 80% (P < 0.05). Similar effects were observed in JGC as ET-1 (10-8 M) significantly reduced basal renin secretion by 26% (P < 0.05). In isolated JGC, isoproterenol increased renin secretion by 151% (P < 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 < 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 < 0.05). In summary, ET-1 directly inhibited basal and isoproterenol-stimulated renin release in both cortical slices and in isolated JGC; the mechanism of this potent inhibition may depend on an increase in intracellular calcium.

Original languageEnglish (US)
Pages (from-to)E521-E525
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume260
Issue number4 23-4
DOIs
StatePublished - 1991

Keywords

  • Angiotensin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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