Norepinephrine and Acetylcholine Transmitter Mechanisms in Large Cerebral Arteries of the Pig

Abstract

This study examines, using an in vitro tissue bath technique, the nature of the transmitter mechanism(s) in the pig cerebral artery. Of the arteries with intact endothelium, about 25% relaxed on application of acetylcholine (ACh) at low concentration (3 × 10−7 to 3 × 10−6 M) and constricted at concentrations exceeding 10−5 M. The remaining arterial preparations either constricted (61%) or exhibited no response (14%) at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M). On the other hand, none of the arteries without endothelium relaxed at any concentration of ACh tested (3 × 10−7 to 3 × 10−3 M); of these, 90% constricted and 10% exhibited no response. These results show that ACh-induced cerebral vasodilation is dependent on endothelial cells and the direct action of ACh on the vascular smooth muscle cells is constriction. Contrary to findings in the large cerebral arteries of the cat and several other species, about 90% of the pig cerebral arteries, with or without endothelium, dilated upon application of norepinephrine (NE) at low concentration (10−7 to 3 × 10−5 M) and constricted at concentrations exceeding 3 × 10−5 M. The NE dose–response relationships were not different in arteries with and without endothelial cells, indicating that the NE-induced vasodilation was independent of the endothelial cells. The relaxation and constriction were blocked by the respective β- and α-receptor antagonists, suggesting that both responses resulted from direct stimulation by NE of β and α receptors on the smooth muscle cells. Transmural nerve stimulation (TNS) consistently induced vasodilation of the arteries whether or not the endothelial cells were present. The vasodilation was abolished by tetrodotoxin (TTX) and cold storage denervation. The TNS-induced vasodilation was not smaller in arteries without endothelium than in those with endothelium. This suggests that TNS-induced vasodilation was independent of the endothelial cells. When examined histochemically, the pig cerebral artery exhibited rich catecholamine fluorescence. Biochemical assays indicate that NE is the primary catecholamine. However, the TNS-induced vasodilation was not affected by atropine, guanethidine, or propranolol, nor prevented by reserpine. It is suggested that an as yet unidentified transmitter is responsible for the TNS-induced vasodilation. Results of this study suggest that the nerve-released ACh is a potential vasoconstrictor transmitter and that NE is a potential vasodilator transmitter in the large cerebral artery of the pig. The neurogenic control of the pig cerebral circulation may be different from that of other species, including humans.