Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats.

Abstract

In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers.