Independent blockade of cerebral vasodilation from acetylcholine and nitric oxide.
We investigated the mechanisms of cerebral arteriolar dilation from topical acetylcholine and the nitrovasodilators, sodium nitroprusside, nitroglycerin, and nitric oxide, in anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. Acetylcholine-mediated dilation was eliminated by topical methylene blue. This blockade was reversed by either topical superoxide dismutase, catalase, or deferoxamine. Nitroprusside- and nitric oxide-induced dilation were not affected by methylene blue. Vasodilation from the nitrovasodilators was significantly diminished by topical nitro blue tetrazolium, but acetylcholine-mediated dilation was unaffected by nitro blue tetrazolium. Neither methylene blue nor nitro blue tetrazolium affected dilation from topical 8-bromoguanosine 3',5'-cyclic monophosphate. These data show that methylene blue selectively blocks acetylcholine-mediated endothelium-dependent dilation by generating oxygen radicals. The mechanism involved is hydroxyl radical-mediated oxidation of endothelium-derived relaxing factor. Nitro blue tetrazolium selectively blocks dilation from the endothelium-independent nitrovasodilators. The endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is not nitric oxide.
Marshall
J J
JJ
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Wei
E P
EP
Kontos
H A
HA
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D009580:Nitroblue Tetrazolium / Q000494:pharmacology; D012016:Reference Values; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D009580:Nitroblue Tetrazolium; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D002374:Catalase; D013482:Superoxide Dismutase; D006152:Cyclic GMP; D003676:Deferoxamine; D000109:Acetylcholine; D008751:Methylene Blue