Nickel inhibits endothelin-induced contractions of vascular smooth muscle.
Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, Ohio 45267.
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Blackburn
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Highsmith
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D016232:Endothelins; D004730:Endothelium, Vascular; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology*; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D016232:Endothelins; D010455:Peptides; D011189:Potassium Chloride; D009532:Nickel