Effects of dotarizine on 45Ca2+ movements and contractile responses in vascular smooth muscle

The inhibitory effects of dotarizine on 45Ca2+ movements and contractile responses were studied and compared, using the same parameters measured in rabbit aorta and basilar smooth muscle. Dotarizine 10(-9)-10(-5) M inhibited the contractile responses induced by high K+ (80 mM), noradrenaline (10(-6) M) or 5-hydroxytryptamine (5-HT, 10(-5) M). These effects were observed when dotarizine was added before or after the induced contractions and were more potent in basilar arteries than in aorta. Moreover, dotarizine at concentrations less than 10(-6) M did not modify the contractile response obtained in aorta rings. Contractile responses induced by the addition of Ca2+ to Ca(2+)-free high-K+ solution were also concentration dependently inhibited by dotarizine 10(-7)-10(-6) M in aorta and basilar arteries. Dotarizine also inhibited the contractile response induced by caffeine (20 mM) in aortic rings incubated in normal or in Ca(2+)-free medium. Dotarizine reduced the 45Ca(2+) uptake stimulated by high K+, noradrenaline or 5-HT even in the aorta or basilar artery, but the inhibition was greater in basilar arteries than in aorta. These results suggest that, in rabbit, dotarizine inhibits Ca2+ entry through Ca2+ channels, being more selective for the basilar artery, probably by acting on multiple sites to decrease the availability of intracellular free Ca2+ required for activation.