Nonprostanoid endothelium-derived factors inhibit renin release.
Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Beierwaltes
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich. 48202-2689.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008555:Melitten / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism; D019323:omega-N-Methylarginine; D000092502:Renin Inhibitors
D001120:Arginine; D016232:Endothelins; D007545:Isoproterenol; D008555:Melitten; D009569:Nitric Oxide; D009599:Nitroprusside; D012083:Renin; D019323:omega-N-Methylarginine; D000092502:Renin Inhibitors