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 X 10(-8) to 3 X 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 (greater than 1 X 10(-3) M) was inhibited by 1 X 10(-9) M and was almost blocked by 3 X 10(-7) M nicardipine. Perivascular nerve stimulation evoked the excitatory junction potential which was slightly suppressed by 3 X 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 (greater than 3 X 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 (greater than 1 X 10(-8) M) to a lesser extent than the K-induced contraction. On the other hand, nicardipine (1 X 10(-6) M) had no effect on the NaCl-free-or 5-hydroxytryptamine-induced contraction. When nicardipine (1 X 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. These results indicate that nicardipine possesses a selective inhibitory action for the Ca channel, but 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.