Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension.
The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anesthetized cats equipped with cranial windows. Superoxide was detected by demonstrating the presence of superoxide dismutase-inhibitable reduction of nitroblue tetrazolium. The superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 4.1 +/- 1.61 nM/min per cm2 during hypertension and 4.55 +/- 0.62 nM/min per cm2 one hour after hypertension had subsided. During norepinephrine administration in the absence of hypertension, the superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 0.44 +/- 0.17 nM/min per cm2. The reduction of nitroblue tetrazolium during hypertension was also inhibited by prior treatment of the brain surface with phenylglyoxal at pH 10, to induce irreversible inhibition of the anion channel. The results show that acute hypertension is associated with the generation of superoxide which enters the extracellular space of the brain via the anion channel. Following hypertension, the sustained vasodilation caused by acute hypertension was inhibited significantly by topical application of superoxide dismutase and catalase, showing that it was due in part to superoxide and other radicals derived from it. The vasodilator response of cerebral arterioles to topical acetylcholine was converted to vasoconstriction following acute hypertension, and restored to vasodilation following topical application of superoxide dismutase and catalase. The results show that superoxide and other radicals generated after acute hypertension interfere with acetylcholine-induced endothelium-dependent vasodilation, probably because they destroy the endothelium-derived relaxant factor.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D009580:Nitroblue Tetrazolium; D002374:Catalase; D013482:Superoxide Dismutase; D000109:Acetylcholine