P10.03 Actions of Verapamil in Producing Vascular Relaxations

We have investigated the vascular relaxant actions of verapamil in comparison with the L-type calcium antagonist nifedipine and the putative selective T-type calcium antagonists NNC 55-0396, mibefradil and thalidomide. Male Wistar rats (250g) were killed by CO2 overdose, the aorta and vas deferens were removed for organ bath studies and rings of tail artery were set up in small vessel myographs. In rat aorta, verapamil (100 uM) significantly reduced the maximum contraction to noradrenaline to a similar degree as nifedipine or mibefradil, but thalidomide had no effect. In rat tail artery, verapamil (1-10 uM) inhibited contractions to calcium restoration both in the presence of phenylephrine and KCl, but the T-type calcium channel blocker NNC 55-0396 (100 uM) inhibited contractions to calcium restoration only in the presence of phenylephrine, and the L-type blocker nifedipine (10 uM) nhibited contractions to calcium restoration only in the presence of KCl. Verapamil inhibited nerve-evoked contractions of epidid-ymal, but not prostatic, portions of rat vas deferens, an action shared with the T-type calcium channel blocker NNC 55-0396 and by thalidomide. In contrast, nifedipine inhibited contractions of prostatic portions of rat vas deferens. It is concluded that verapamil produces vascular relaxations by a mechanism that involves aspects of both L-type and T-type calcium channel block.