NITRIC-OXIDE AND S-NITROSO-L-CYSTEINE AS ENDOTHELIUM-DERIVED RELAXINGFACTORS FROM ACETYLCHOLINE IN CEREBRAL VESSELS IN CATS

Background and Purpose: The predominant view is that the endothelium-d erived relaxing factor generated by acetylcholine from blood vessels i s nitric oxide. However, there is evidence suggesting that certain nit ric oxide-containing compounds such as nitrosothiols resemble the endo thelium-derived relaxing factor generated by acetylcholine more closel y than does nitric oxide itself. Accordingly, we compared the effects of nitric oxide and S-nitroso-L-cysteine on cerebral arteriolar calibe r in relation to the associated increments in nitrite concentration in the effluent. Methods. Acetylcholine, nitric oxide, and S-nitroSo-L-c ysteine were administered by continuous superfusion in oxygen-five sol ution through the space under a cranial window in anesthetized cats. N itrite concentration was measured in the effluent. The degree of vasod ilation induced was evaluated in relation to the increment in nitrite concentration. Results. All agents induced dose-dependent vasodilation and dose-dependent increments in nitrite concentration in the effluen t. For any given degree of vasodilation, the increments in nitrite con centration were equivalent during acetylcholine or S-nitroso-L-cystein e infusion, whereas the nitrite concentrations were 10 times higher du ring nitric oxide infusion. After administration of nitroarginine, a c ompetitive inhibitor of nitric oxide synthesis from arginine, there wa s depression in the vasodilation as well as the increment in nitrite c oncentration induced by acetylcholine. Conclusions: S-NitroSo-L-cystei ne resembles endothelium-derived relaxing factor from acetylcholine mo re closely than does nitric oxide.