ABSTRACT
The effects of the new calcium blocker (CAB), bepridil hydrochloride (BP), on calcium influx and isometric tension development resulting from activation of both the potential-dependent (60 mM KCl) and the receptor-operated (10 microM norepinephrine) calcium channel were studied in rings of rabbit thoracic aorta. BP was compared to nifedipine (NF), verapamil hydrochloride (VP) and diltiazem hydrochloride (DZ). The effects of the CABs were compared to those of alpha-1 adrenergic receptor blocker, prazosin (0.01, 0.1 and 10.0 microM), and to those of the inorganic nonspecific calcium channel blocker, lanthanum chloride (0.1, 1.0 and 5.0 mM). All organic CABs tested between 0.1 and 10.0 microM significantly inhibited potential-dependent activity with respect to both calcium influx and development of isometric tension (NF greater than BP = VP greater than DZ). However, only BP additionally inhibited both aspects of receptor-operated activity in a concentration-dependent fashion. In an isolated guinea-pig Langendorff heart preparation, all CABs increased coronary flow (NF greater than DZ greater than BP = VP) and reduced cardiac contractile force (VP = NF greater than DZ greater than BP) without significantly altering spontaneous rate. In the absence of extracellular calcium ion (0 calcium solution + 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid), norepinephrine caused a phasic contractile response in rabbit thoracic aorta which was suppressed by VP and NF but not by DZ or BP. These results suggest that the four calcium blockers have differential effects on calcium channel activity and on intracellular calcium release in vascular smooth muscle.
Subject(s)
Calcium Channel Blockers/pharmacology , Calcium/metabolism , Ion Channels/drug effects , Muscle, Smooth, Vascular/drug effects , Pyrrolidines/pharmacology , Action Potentials/drug effects , Animals , Aorta/drug effects , Bepridil , Coronary Circulation/drug effects , Guinea Pigs , Male , Muscle Contraction/drug effects , Myocardial Contraction/drug effects , Norepinephrine/pharmacology , RabbitsABSTRACT
This study was designed to determine whether neuroleptic drugs have calcium channel blocking activity in isolated rings of rabbit thoracic aorta. The results confirm previous findings that pimozide and penfluridol are calcium channel blockers. However, the data do not support the conclusion that these agents are selective for the voltage-sensitive calcium channel. The results also show that both haloperidol and chlorpromazine (which represent different classes of neuroleptic drugs) are also calcium channel blockers in vascular smooth muscle.
