Nicorandil (2-nicotinamidoethyl nitrate) inhibits both vaso-dilating and -constricting effects of endothelin in a vascularly isolated hind-limb preparation in rats.
Effects of nicorandil (2-nicotinamidoethyl nitrate), a nitrate derivative with a K+ channel-opening action, on endothelin-1 (ET)-induced effects on peripheral blood vessels were studied using a hind-limb perfusion preparation in rats. ET injected into this circuit increased the perfusion pressure for more than 30 min following a transient, initial vasodepression of the perfusion system. The magnitude of both responses was dose-dependent. Pretreatments with nicorandil infused into this preparation significantly attenuated both the initial vasodilation and the sustained vasoconstriction caused by ET. The initial vasodepression caused by ET could be mediated by the release of endothelium-derived relaxing factor (EDRF). The sustained phase would be due to increased intracellular calcium elicited by ET. Nicorandil inhibited both the initial and the sustained phase of the ET-responses, probably by inhibition of intracellular phosphoinositide metabolism in both endothelium and vascular smooth muscle cells.
Nishimura
M
M
Department of Clinical Laboratory and Medicine, Kyoto Prefectural University of Medicine, Japan.
Takahashi
H
H
Sakamoto
M
M
Ikegaki
I
I
Nakanishi
T
T
Yoshimura
M
M
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; D016232:Endothelins; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D002118:Calcium