Electrical responses of smooth muscle cells during cholinergic vasodilation in the rabbit saphenous artery

Isolated smooth muscle tissues of the rabbit saphenous artery precontracted with norepinephrine (NE) were relaxed by acetylcholine (ACh, greater than 10(-7) M) or oxotremorine (greater than 10(-7) M), through the activation of muscarinic receptors, only when the endothelial cells were intact. ACh (greater than 10(-7) M) transiently hyperpolarized the membrane (1-4 minutes) with an associated decrease in the membrane resistance, either in the presence or absence of NE, and these changes ceased during the continuous application of ACh. The ACh-induced transient hyperpolarization was not generated after mechanically removing the endothelium or by treatment with atropine. Oxotremorine (up to 10(-5) M) did not alter the membrane potential in the presence or absence of the endothelium. NE (10(-6) M) depolarized the smooth muscle membrane, which remained unchanged by additional application of ACh or oxotremorine for more than 5 minutes, or after removal of the endothelium. The excitatory junction potential generated by perivascular nerve stimulation was inhibited by ACh (greater than 10(-9) M) or oxotremorine (greater than 10(-9) M) in a concentration-dependent manner. These inhibitory actions of ACh or oxotremorine were blocked by atropine but were not affected by removal of the endothelial cells. These results suggest that the inhibitory actions of muscarinic agonists on electrical responses of smooth muscle cells of the rabbit saphenous artery were mainly indirect, i.e., a release of inhibitory substances from the endothelial cells and the inhibition of adrenergic transmission. The former required higher concentrations of ACh or oxotremorine, thereby suggesting that the latter may be more important for vasodilation related to cholinergic mechanisms.