title: Inhibitors of calmodulin impair the constitutive but not the inducible nitric oxide synthase activity in the rat aorta.
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.
authors.affiliation: Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
authors.forename: V B
authors.initials: VB
authors.lastname: Schini
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D006152:Cyclic GMP / Q000096:biosynthesis; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005275:Fendiline / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002147:Calmodulin; D007093:Imidazoles; D014665:Vasodilator Agents; D019335:Nitroarginine; C031938:calmidazolium; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D005275:Fendiline