NICARDIPINE ACTIONS ON SMOOTH-MUSCLE CELLS AND NEUROMUSCULAR-TRANSMISSION IN THE GUINEA-PIG BASILAR ARTERY

Abstract

The effects of nicardipine on smooth muscle cells of the guinea pig basilar artery were investigated by means of microelectrode and isometric tension recording methods. Nicardipine (1 .times. 10-8-3 .times. 10-6 M) did not modify the membrane potential and resistance of smooth muscle cells. The spike evoked by application of outward current pulse in the presence of tetraethylammonium (> 1 .times. 10-3 M) was inhibited by 1 .times. 10-9 M and was almost blocked by 3 .times. 10-7 M nicardipine. Perivascular nerve stimulation evoked the excitatory junction potential which was slightly suppressed by 3 .times. 10-6 M nicardipine. The contractions evoked by excess concentration of [K]0, NaCl-free solution or ATP was abolished and by 5-hydroxytryptamine was markedly inhibited in Ca-free ethylene glycol bis(.beta.-aminoethyl ether)N,N,''-tetracetic acid-containing solution, but that induced by caffeine was only slightly inhibited. Nicardipine (> 3 .times. 10-10 M) markedly inhibited the K-induced contraction noncompetitively as estimated from the Lineweaver-Burk''s plot. The ATP-induced contractions were slightly inhibited by nicardipine (> 1 .times. 10-8 M) to a lesser extent than the K-induced contraction. Nicardipine (1 .times. 10-6 M) had no effect on the NaCl-free- or 5-hydroxytryptamine-induced contraction. When nicardipine (1 .times. 10-6 M) was applied during 2.5 mM Ca loading to muscle cells after depletion of the stored Ca, the subsequently generated caffeine-induced contraction was slightly inhibited due to inhibition of the passive Ca influx. Nicardipine evidently possesses a selective inhibitory action for the Ca channel; the inhibition is limited to particular Ca influxes such as the voltage-dependent one, but not the receptor operated and NaCl-free-induced Ca influxes. This agent acts predominantly on the postjunctional muscle rather than the prejunctional nerve terminal.