The inhibitory effects of calmodulin antagonists on the endothelium-dependent relaxation in rabbit aorta.
Effects of trifluoperazine (TFP, 10(-5) M), trifluoperazine sulfoxide (TFP-SO, 10(-5) M), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7-, 10(-4) M), N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5, 10(-4) M) and verapamil (10(-5) M) on the endothelium-dependent relaxation of the contractions induced in the isolated rabbit aorta were studied. Carbachol (10(-6) - 10(-6) M) and A23187 (10(-8) M) relaxed the contraction due to norepinephrine (10(-6) M and histamine (10(-5) M) in the aorta with endothelium. TFP and W-7 completely inhibited the relaxation induced by carbachol and A23187. In contrast, TFP-SO and W-5, which have lower affinity to calmodulin, had little or no effect on either the carbachol- or A23187-induced relaxation. An organic calcium antagonist, verapamil, did not change the relaxation induced by carbachol or A23187. W-7 did not modify the relaxing effect of sodium nitroprusside (10(-8) - 10(-6) M) which is not mediated by endothelium. These results suggest that either formation or release of endothelium-derived relaxing factor involves the process mediated by calmodulin in the rabbit aorta.
D000818:Animals; D001011:Aorta; D000001:Calcimycin / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002217:Carbachol / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide; D011817:Rabbits; D014268:Trifluoperazine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D002147:Calmodulin; D014665:Vasodilator Agents; D014268:Trifluoperazine; D009569:Nitric Oxide; D000001:Calcimycin; D002217:Carbachol; D014700:Verapamil