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.