Pharmacological properties of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist in arterial strips from rats and rabbits

Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist on vascular smooth muscle contraction were determined with helically cut arterial strips from rats and rabbits, since adrenergic innervation is quite different between the two species. The pD2 value of W-7-induced relaxation was significantly larger in rat aorta than in rabbit aorta. Treatment of the rabbit aorta with phenoxybenzamine, an alpha adrenoceptor antagonist, augmented the W-7 induced relaxation, whereas in rat aorta there was no such augmentation. Media-intimal strips of rabbit aorta showed a larger pD2 value of W-7 as compared to the value seen with whole aorta. The pD2 values of W-7 obtained in phenoxybenzamine-treated and media-intimal strips of rabbit aorta were in good agreement with the value obtained in rat aorta. Aortic strip contraction induced by W-7, which has been demonstrated as a calmodulin-independent effect of this compound, was significantly smaller in rats than in rabbits, suggesting that the relaxation of rabbit aorta induced by W-7 was inhibited by its own contractile effect. W-7 exhibited a typical noncompetitive antagonism against both norepinephrine- and Ca++- (K+-depolarized muscle) induced contractions, and the potency of antagonism was similar between the two agonists. W-7 did not affect 5-min 45Ca incubation value of the K+-stimulated increase in cellular Ca++ content in rabbit aorta, while trifluoperazine, another calmodulin antagonist, and D-600, a calcium antagonist, reduced this value.(ABSTRACT TRUNCATED AT 250 WORDS)