Effect of Nolinium Bromide on Vascular Smooth Muscle

Abstract

Abstract

Nolinium bromide inhibits gastric acid secretion and gastrointestinal smooth muscle contraction. While the compound's gastric antisecretory action has been attributed in part to inhibition of gastric adenylate cyclase and the gastric proton-transport ATPase, the mechanism of nolinium bromide's relaxant effect on smooth muscle has not been elucidated. We have determined that nolinium bromide inhibits contraction of vascular smooth muscle, using isolated rabbit aortic strips. This report characterizes the specificity of this inhibition (by using several agonists) and its Ca²⁺ dependence (by using contractile conditions of known dependence on various Ca²⁺ pools). Nolinium bromide (50-200 μM) was a reversible, insurmountable inhibitor of contractions induced by Ca²⁺ (in 40 mM KCl depolarizing medium) and norepinephrine, with IC₅₀ values of 96 and 118 μM, respectively, for suppression of maximum contractile force. Contractions in response to Asn¹Val⁵-angiotensin II in both 2.5 mM Ca²⁺ and 0 mM Ca²⁺ medium were also inhibited (IC₅₀ value = 110 μM under both conditions). Initial contraction rates for all these conditions were depressed by nolinium bromide. Nolinium bromide inhibited equally the phasic (internal Ca²⁺-dependent) and tonic (external Ca²⁺-dependent) components of norepinephrine-induced contractions. These results extend the muscle relaxant profile of nolinium bromide to include, albeit with low potency, vascular smooth muscle, and show that its potency is similar in inhibiting the contractile response to three different stimuli: angiotensin II, Ca²⁺, and norepinephrine.