Light-induced vs. bradykinin-induced relaxation of coronary arteries: Do S-nitrosothiols act as endothelium-derived hyperpolarizing factors?

BACKGROUND: Light-induced relaxation depends on S-nitrosothiols. S-Nitrosothiols may also serve as endothelium-derived hyperpolarizing factors, mediating the relaxant response of porcine coronary arteries (PCAs) to bradykinin. Here we compared the mechanism of light-induced and bradykinin-induced PCA relaxation. METHODS: PCAs were mounted in organ baths in the dark, preconstricted and exposed to polychromatic light (5 min) or 100 nmol/l bradykinin. RESULTS: Light relaxed PCAs by maximally 71 ± 1%. S-Nitrosothiol depletion abolished this relaxation. Relaxations diminished following repetitive light exposures, particularly if the dark periods between the light exposures were less than 10 min, and increased following endothelium removal or nitric oxide synthase blockade with N-nitro-L-arginine methyl ester (L-NAME), despite the prevention of guanosine-3′,5′-cyclic monophosphate generation by the latter two procedures. Thus, reloading of the storage pools occurs in the dark, endothelial nitric oxide inhibits this process and photorelaxation does not depend on guanosine-3′,5′-cyclic monophosphate. Bradykinin relaxed PCAs by 69 ± 3%. The nitric oxide scavenger hydroxocobalamin and the Na-K ATPase inhibitor ouabain abolished the responses to bradykinin and light. The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one abolished the response to light, and, like L-NAME, blocked the response to bradykinin by more than 50%. On top of L-NAME, intermediate and small conductance Ca-dependent K channel (IKCa/SKCa) blockade further reduced the response to bradykinin and enhanced photorelaxation. CONCLUSION: Photorelaxation depends on stored S-nitrosothiols and their release/synthesis is negatively affected by endothelial nitric oxide and IKCa/SKCa. S-Nitrosothiols activate endothelial IKCa/SKCa and, via guanylyl cyclase, smooth muscle Na-K ATPase. Thus, they possess all properties of a bradykinin-induced endothelium-derived hyperpolarizing factor.

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