Nicardipine actions on smooth muscle cells and neuromuscular transmission in the guinea pig basilar artery.

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 (1×10−8−3×10−6M) 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 (>1×10−3M) was inhibited by 1x10−9M and was almost blocked by 3×10−7M nicardipine. Perivascular nerve stimulation evoked the excitatory junction potential which was slightly suppressed by 3×10−6M nicardipine. The contraction evoked by excess concentration of [K], NaCl-free solution or ATP was abolished and by 5-hydroxytryptamine (5-HTJ was markedly inhibited in Ca-free EGTA containing solution, but that induced by caffeine was only slightly inhibited. Nicardipine (>3×10−10M) markedly inhibited the K-induced contraction. The ATP induced contractions were inhibited by nicardipine (>1×10−8M) to a lesser extent than the K-induced contractions. On the other hand, nicardipine (1×10−6M) had no effect on the NaCl-free- or 5-HT-induced contraction. When nicardipine (1×10−6M) was applied during 2.5mM Ca loading to muscle cells after depletion of the stored Ca, the subsequently generated caffeine-induced contraction was slightly depressed due to inhibition of the passive Ca influx. These results indicate that nicardipine possesses a selective inhibitory action on the Ca channel, but that the inhibition is limited to particular Ca influxes such as the voltage dependent ones, but not the receptor operated and NaCl-free induced Ca influxes. This agent acts predominantly on the post-junctional muscle rather than on the prejunctional nerve terminal.