Modulation of norepinephrine-induced vasoconstriction by endothelin-1 and nitric oxide in rat tail artery.
The effects of endothelin-1 (ET-1) and an inhibitor of the synthesis of nitric oxide (NO) have been examined on vasoconstrictor responses to nerve stimulation and norepinephrine in the rat isolated perfused tail artery. In endothelium-denuded preparations, a 60-min exposure to 0.3 nM ET-1 had no effect on the basal perfusion pressure, but significantly enhanced responses to stimulation (1 Hz, 10 s) and norepinephrine (10 ng) to 124 +/- 9% (n = 6) and 139 +/- 14% (n = 8), respectively, of control responses. In endothelium-intact preparations, inhibition of NO synthesis by NG-nitro-L-arginine (NOLA, 10 microM) enhanced responses to stimulation (5 Hz, 10 s) and norepinephrine (10 ng) to 171 +/- 12% (n = 6) and 222 +/- 9% (n = 4), respectively, of control responses. The NOLA-induced enhancements were prevented by 100 microM L-arginine but not by 100 microM D-arginine, and did not occur in endothelium-denuded arteries. In other experiments, segments of rat tail artery were perfused in a low-volume (3.5 ml) recirculating system. The basal perfusion pressure was consistent for at least 60 min. In endothelium-denuded segments, vasoconstrictor responses to nerve stimulation (0.5 Hz, 10 s) or norepinephrine (10 ng) remained constant. However, in endothelium-intact segments, responses to stimulation and norepinephrine gradually increased to 158 +/- 13% (n = 6) and 152 +/- 8% (n = 5), respectively, of initial responses, after 45 min of recirculation. The increases were not related to NO, as they remained unchanged in the presence of 10 microM NOLA. Thus, it appears that a vasoconstriction-enhancing factor, possibly ET-1, is released from endothelial cells and accumulates in the perfusion fluid.
Reid
J J
JJ
Department of Pharmacology, University of Melbourne, Australia.
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Lieu
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Wong-Dusting
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Rand
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MJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D009638:Norepinephrine