The mechanism of vasodilation induced by fentanyl was investigated using isolated rat thoracic aortic rings. Rings were contracted with norepinephrine(10-E-7 M, NE) and potassium chloride(40 mM, KCI) with and without endothelium. Fentanyl
(10E-9-10E-5
M) produced dose-dependent relaxation and had no significant effect from endothelium(intact and denuded rings, test with 3×10E-4 M LNAME, NQ-nitro-L-arginine methyl ester). Pretreatment of indomethacin(2.5×10E-5 M, inhibitor of cyclooxygenase)
failed
to influence of cumulative dose-response curves. RD50(50% relaxation dose) and KCI/NE ratio as potency difference of fentanyl, verapamil(10E-8-10E-5 M, Ca2+ channel blocker), nitroglycerin(10E-10-10E-5 M, activator of guanylate cyclase) were not
similar.
Fentanyl and control(distilled waster) were not demonstrated any different contraction produced by incremental addition of Ca2+ to aortic rings exposed to Ca2+ free, K+-depolarized(100 mM CKI) solution(extracellular Ca2+ influx). But fentanyl had
effect
on intracelular Ca2+ free solution.
We conclude that, in rat aorta, fentanyl-induced relaxation is endothelium-independent but mediated by inhibition of alpha-adrenoceptors operated intracellular Ca2+ release (inhibition of contraction by NE) and caffeine-induced Ca2+ release from
store.
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