TY - JOUR T1 - Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 553 LP - 559 VL - 261 IS - 2 AU - V B Schini AU - P M Vanhoutte Y1 - 1992/05/01 UR - http://jpet.aspetjournals.org/content/261/2/553.abstract N2 - The possibility that calmodulin inhibitors impair the constitutive but not the inducible nitric oxide synthase(s)-mediated inhibitions of tone was investigated in the rat aorta. The endothelium-dependent relaxations evoked by acetylcholine, ATP and the calcium ionophore A23187 (which are mediated by the constitutive nitric oxide synthase) were inhibited by calmodulin inhibitors [calmidazolium, W-7 and (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, hydrochloride, fendiline] and by an inhibitor of nitric oxide synthase, nitro L-arginine. Nitro L-arginine but not calmidazolium reduced the inhibitory influence of the endothelium on the concentration-contraction curves evoked by phenylephrine. Treatment of aortic rings without endothelium with interleukin-1 beta inhibited the contractions to phenylephrine by inducing nitric oxide synthase activity. Nitro L-arginine but not calmidazolium restored the contractility of the aortic rings. The relaxations evoked by a donor of nitric oxide, 3-morpholino-sydnonimine, were minimally affected by calmidazolium and nitro L-arginine. The basal tissue content in, and the production of, guanosine 3',5' cyclic monophosphate evoked by acetylcholine in rings with endothelium were inhibited by calmidazolium and nitro L-arginine. The production of cyclic GMP evoked by interleukin-1 beta in rings without endothelium was inhibited by nitro L-arginine but not by calmidazolium. These observations indicate that calmodulin inhibitors inhibit the constitutive but not the inducible nitric oxide synthase(s) in the rat aorta. ER -