Endothelium-derived relaxing factor modulates endothelin action in afferent arterioles.
Endothelin is a potent vasoconstrictor, whereas endothelium-derived relaxing factor (EDRF) is a potent vasodilator. Both are produced by the endothelium. Although they have been studied extensively in large vessels, little is known about their actions in renal microvessels. Using microdissected rabbit afferent arterioles, we studied the vascular response to synthetic endothelin and its interaction with EDRF and the effect of endothelin on renin release. Afferent arterioles were either microperfused in vitro at 60 mm Hg to measure luminal diameter or incubated without microperfusion to assess renin release. When added to the bath, 10(-10) or 10(-9) M endothelin decreased the diameter by 32 +/- 8% (n = 7, p less than 0.01) or 76 +/- 7% (p less than 0.0001), respectively. Pretreatment with Nw-nitro L-arginine, which inhibits synthesis of EDRF, decreased basal diameter by 15 +/- 1% (p less than 0.001) and augmented endothelin-induced constriction; decrease in diameter with 10(-10) M endothelin was 78 +/- 10% (n = 4, p less than 0.01 versus nontreated). In afferent arterioles preconstricted by endothelin, acetylcholine at concentrations of 10(-8) to 10(-5) M increased the diameter in a dose-dependent manner. Basal renin release was 0.62 +/- 0.15 ng angiotensin I/hr/afferent arterioles/hr (n = 13) and was not affected by endothelin (10(-10) to 10(-6) M). Increase in renin release by isoproterenol was the same in afferent arterioles pretreated with vehicle or endothelin (10(-7) M; delta, 0.49 +/- 0.21 versus 0.42 +/- 0.19; n = 13).(ABSTRACT TRUNCATED AT 250 WORDS)
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Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI 48202.
Juncos
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Nushiro
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Johnson
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Carretero
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019335:Nitroarginine; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000378:metabolism; D014661:Vasoconstriction
D016232:Endothelins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D012083:Renin; D007545:Isoproterenol; D000109:Acetylcholine