Mechanisms that produce nitric oxide-mediated relaxation of cerebral arteries during atherosclerosis.

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Abstract
Background and Purpose —The first goal of the present study was to examine the hypothesis that relaxation of cerebral arteries to nitric oxide in primates is dependent on activation of soluble guanylate cyclase (sGC). The second goal was to determine whether the role of sGC in mediating responses to nitric oxide is altered in atherosclerosis. Methods —Basilar arteries from normal and atherosclerotic monkeys were studied in vitro. After precontraction with prostaglandin F 2α (0.1 to 1 μmol/L), concentration-response curves to authentic nitric oxide (1 nmol/L to 1 μmol/L), sodium nitroprusside (10 nmol/L to 10 μmol/L; a nitric oxide donor), and papaverine (10 nmol/L to 10 μmol/L; a non–nitric oxide, non–sGC-dependent stimulus) were generated in the presence and absence of 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 and 10 μmol/L; an inhibitor of sGC). The effect of ODQ on basal tone of basilar arteries from normal and atherosclerotic monkeys was also examined. Results —Nitric oxide, sodium nitroprusside, and papaverine produced relaxation that was similar ( P >0.05) in normal and atherosclerotic monkeys. ODQ produced marked inhibition ( P P 2α was similar in the basilar artery from normal and atherosclerotic monkeys. Conclusions —These findings suggest that (1) relaxation of cerebral arteries in primates in response to nitric oxide is normally dependent, in large part, on activation of sGC and (2) the influence of sGC (via reduced production and/or activity of basal nitric oxide) on cerebral vascular tone is reduced in atherosclerosis.

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