CEREBRAL BLOOD-FLOW AND CEREBROVASCULAR REACTIVITY AFTER INHIBITION OF NITRIC-OXIDE SYNTHESIS IN CONSCIOUS GOATS

1 The role of nitric oxide in the cerebral circulation under basal con ditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nit ric oxide production with N-nitro-L-arginine methyl ester (L-NAME). 2 In 6 unanaesthetized goats, blood flow to one brain hemisphere (electr omagnetically measured), systemic arterial blood pressure and heart ra te were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decre ased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebro vascular resistance increased by 114 +/- 13% (P<0.01); the immediate a ddition of i.v. infusion of L-NAME (0.15-0.20 mg kg-1 during 60-80 min ) did not significantly modify these effects. Cerebral blood flow reco vered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3 A second treatme nt With L-NAME scheduled as above reproduced the immediate haemodynami c effects of the first treatment, which (except bradycardia) reversed with L-arginine (200-300 mg kg-1 by i.v. bolus). 4 Acetylcholine (0.01 -0.3 mug), sodium nitroprusside (3-100 mug) and diazoxide (0.3-9 mg), injected into the cerebral circulation of 5 conscious goats, produced dose-dependent increases in cerebral blood flow, and decreases in cere brovascular resistance; sodium nitroprusside (30 and 100 mug) also cau sed hypotension and tachycardia. 5 The reduction in cerebrovascular re sistance from resting levels (in absolute values) to lower doses, but not to the highest dose, of acetylcholine was diminished, to sodium ni troprusside was increased, and to diazoxide was unaffected after L-NAM E, compared to control conditions. The effects on cerebrovascular resi stance to acetycholine normalized within 24 h and to sodium nitropruss ide within 48 h after L-NAME treatment. 6 This study provides informat ion about the evolution of the changes in cerebral blood flow and cere brovascular reactivity after inhibition of endogenous nitric oxide in conscious animals. The results suggest: (a) endogenous nitric oxide is involved in regulation of the cerebral circulation by producing a res ting vasodilator tone, (b) the cerebral vasodilatation to acetylcholin e is mediated, at least in part, by nitric oxide release, and (c) inhi bition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.