Effects of oxodipine on 45Ca movements and contractile responses in vascular smooth muscle

Abstract

1. The inhibitory effects of oxodipine, a new dihydropyridine, were compared with those of nifedipine on contractile responses in rat isolated aortic strips and on spontaneous mechanical activity in portal vein segments. 2. In rat isolated aorta oxodipine (IC50 = 7.8 +/- 1.8 x 10(-9)M) and nifedipine (IC50 = 8.5 +/- 2.5 x 10(-9)M) dose-dependently inhibited the contractile responses induced by high K (80 mM), whereas responses to noradrenaline (NA, 10(-6)M) were only slightly affected (IC50 greater than 10(-7)M). These inhibitory actions were observed with both drugs added either before or after the induced contractions. 3. Contractile responses induced by addition of Ca to 0Ca high-K solution were also dose-dependently inhibited by oxodipine (IC50 = 4.5 +/- 2.5 x 10(-9)M). However, oxodipine up to 10(-6)M did not modify the contractile responses obtained in strips incubated in 0Ca when Ca was added in the presence of NA. 4. Oxodipine and nifedipine also inhibited the development of spontaneous mechanical activity in portal vein segments. 5. Oxodipine inhibited 45Ca uptake stimulated by high K (I50 = 8.7 +/- 2.5 x 10(-9)M) or by NA (I50 greater than 10(-7)M). However, it did not modify 45Ca uptake and 45Ca efflux in resting strips or 45Ca efflux stimulated by NA. 6. These results indicate that the effects of oxodipine on vascular smooth muscle may be due to the blockade of Ca entry through potential- and receptor-operated channels; it was at least 10 times more selective for potential-operated channels. Oxodipine did not modify Ca entry through passive leak channels and NA-induced intracellular Ca release.