EFFECTS OF DOTARIZINE ON CA-45(2-MUSCLE() MOVEMENTS AND CONTRACTILE RESPONSES IN VASCULAR SMOOTH)

The inhibitory effects of dotarizine on Ca-45(2+) movements and contra ctile responses were studied and compared, using the same parameters m easured in rabbit aorta and basilar smooth muscle. Dotarizine 10(-9)-1 0(-5) M inhibited the contractile responses induced by high K+ (80 mM) , noradrenaline (10(-6) M) or 5-hydroxytryptamine (5-HT, 10(-5) M). Th ese effects were observed when dotarizine was added before or after th e induced contractions and were more potent in basilar arteries than i n aorta. Moreover, dotarizine at concentrations less than 10(-6) M did not modify the contractile response obtained in aorta rings. Contract ile responses induced by the addition of Ca2+ to Ca2+-free high-K+ sol ution were also concentration dependently inhibited by dotarizine 10(- 7)-10(-6) M in aorta and basilar arteries. Dotarizine also inhibited t he contractile response induced by caffeine (20 mM) in aortic rings in cubated in normal or in Ca2+-free medium. Dotarizine reduced the Ca-45 (2+) uptake stimulated by high K+, noradrenaline or 5-HT even in the a orta or basilar artery, but the inhibition was greater in basilar arte ries than in aorta. These results suggest that, in rabbit, dotarizine inhibits Ca2+ entry through Ca2+ channels, being more selective for th e basilar artery, probably by acting on multiple sites to decrease the availability of intracellular free Ca2+ required for activation.