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Abstract

Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.

V B Schini and P M Vanhoutte
Journal of Pharmacology and Experimental Therapeutics May 1992, 261 (2) 553-559;
V B Schini
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P M Vanhoutte
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Abstract

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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 261, Issue 2
1 May 1992
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Abstract

Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.

V B Schini and P M Vanhoutte
Journal of Pharmacology and Experimental Therapeutics May 1, 1992, 261 (2) 553-559;

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Abstract

Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.

V B Schini and P M Vanhoutte
Journal of Pharmacology and Experimental Therapeutics May 1, 1992, 261 (2) 553-559;
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