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

Background and Purpose: The predominant view is that the endothelium-derived relaxing factor generated by acetylcholine from blood vessels is nitric oxide. However, there is evidence suggesting that certain nitric oxide-containing compounds such as nitrosothiols resemble the endothelium-derived relaxing factor generated by acetylcholine more closely than does nitric oxide itself. Accordingly, we compared the effects of nitric oxide and S-nitroso-L-cysteine on cerebral arteriolar caliber in relation to the associated increments in nitrite concentration in the effluent. Methods. Acetylcholine, nitric oxide, and S-nitroSo-L-cysteine were administered by continuous superfusion in oxygen-five solution through the space under a cranial window in anesthetized cats. Nitrite concentration was measured in the effluent. The degree of vasodilation 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 effluent. For any given degree of vasodilation, the increments in nitrite concentration were equivalent during acetylcholine or S-nitroso-L-cysteine infusion, whereas the nitrite concentrations were 10 times higher during nitric oxide infusion. After administration of nitroarginine, a competitive inhibitor of nitric oxide synthesis from arginine, there was depression in the vasodilation as well as the increment in nitrite concentration induced by acetylcholine. Conclusions: S-NitroSo-L-cysteine resembles endothelium-derived relaxing factor from acetylcholine more closely than does nitric oxide.