Abstract
The effect of SG-75 (Nicorandil) on the neuromuscular transmission and smooth muscle membrane of the rabbit ear artery was investigated by means of intracellular microelectrodes, isometric tension recording and flux experiments. This agent caused a pronounced hyperpolarization of the cell membrane and a significant increase of the K-permeability. During perivascular nerve stimulation, the amplitude and the time constant of the falling phase of the excitatory junction potentials were reduced, causing a suppression of spike generation and of the concomitant contractile responses, but the release of [3H]noradrenaline was not affected. At high doses this agent inhibited significantly submaximal contractile responses induced by various stimuli. However, these effects could not be correlated with changes in 45Ca fluxes. It is suggested that although the effect of SG-75 could be due mainly to an increase of the K-permeability and the concomitant hyperpolarization, it might also reduce the force development by a mechanism which does not depend on a reduction of the concentration of ionized Ca in the cytoplasm.
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