Cholinergic mechanism in the large cat cerebral artery.

The isolated cat cerebral arteries (basilar, middle cerebral, anterior cerebral, and internal carotid) were studied in vitro. ACh at low concentration (3 x 10(-8) to 3 x 10(-6) M) induced relaxation, and at high concentration (10(-5) to 3 x 10(-3) M) induced constriction of the arteries with endothelial cells. In contrast, concentration of any magnitude (10(-6) to 3 x 10(-3) M) induced constriction exclusively in arteries without endothelium. Atropine (3 x 10(-6) to 3 x 10(-5) M) blocked and physostigmine (3 x 10(-6) M) potentiated both ACh-induced relaxation and constriction. These results suggest that the relaxation induced by exogenous ACh is solely dependent on the endothelial cells and that the primary effect of the direct action of ACh on the smooth muscle cells is constriction. Transmural nerve stimulation (TNS) induced a frequency-dependent relaxation in the arteries with or without endothelium. Neither atropine nor physostigmine affected the TNS-induced dilator response in either preparation. This, together with the wide separation between the nerve and endothelium in the vessel wall, suggests that ACh is not involved in TNS-induced vasodilation. Furthermore, the TNS-induced relaxation at any frequency is not smaller but greater in the arteries without endothelial cells than in those with endothelial cells. Blockade of the TNS-induced vasodilation by tetrodotoxin (TTX) or cold storage denervation did not prevent the arteries from relaxing in response to ACh or methacholine (MCh). It is suggested that the TNS-induced vasodilation is independent of the endothelial cells and that the vasodilation is due to the direct action of a yet-to-be identified dilator transmitter on the smooth muscle cells. Results of the present study support our previous finding that, in the cat cerebral artery. ACh is more likely to be a constrictor transmitter than a dilator transmitter.