VIP-ergic and cholinergic innervations in internal carotid arteries of the cat and rat.

Using immunohistochemical methods, choline acetyltransferase and vasoactive intestinal polypeptide immunoreactive (ChAT-I and VIP-I) fine fibers with varicosity-like structures were observed in the rat and cat cerebral arteries. Acetylcholine (ACh) induced dual responses in endothelium-intact internal carotid arteries of the cat; it induced vasodilation at low concentrations and constrictions at high concentrations (greater than 10(-6) M). ACh induced contraction exclusively in endothelium-rubbed preparations. Atropine (10(-7) M) blocked ACh-induced constriction and dilatation. ACh-induced vasodilation was potentiated by M & B 22,948 (2 x 10(-5) M), a selective cyclic GMP phosphodiesterase inhibitor. Vasoconstriction induced by ACh was inhibited by neomycin (3 x 10(-3) M), an inositol phosphate synthesis inhibitor, which did not affect the neuropeptide Y-induced contraction. VIP-induced dilation of the cat internal carotid arteries was not affected by removing the endothelial layer, but was blocked by VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) and potentiated by cilostazol (2 x 10(-5) M), a selective cyclic AMP phosphodiesterase inhibitor. These results are consistent with previous findings that cerebral blood vessels receive cholinergic and VIP-ergic innervations, and that ACh-induced endothelium-dependent vasodilation is mediated by cyclic GMP synthesis, and that VIP-induced endothelium-independent vasodilation is mediated by cyclic AMP synthesis. The present study, however, demonstrates for the first time the presence of varicosity-like structure associated with ChAT-I fibers, suggesting the presence of cholinergic nerve terminals and that ACh-induced cerebral vasoconstriction is mediated by phosphatidyl-inositide turnover.