title: Cerebral blood flow and cerebrovascular reactivity after inhibition of nitric oxide synthesis in conscious goats.
abstract: 1. The role of nitric oxide in the cerebral circulation under basal conditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 6 unanaesthetized goats, blood flow to one brain hemisphere (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decreased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebrovascular resistance increased by 114 +/- 13% (P < 0.01); the immediate addition 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 recovered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3. A second treatment with L-NAME scheduled as above reproduced the immediate haemodynamic 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 micrograms), sodium nitroprusside (3-100 micrograms) 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 cerebrovascular resistance; sodium nitroprusside (30 and 100 micrograms) also caused hypotension and tachycardia. 5. The reduction in cerebrovascular resistance from resting levels (in absolute values) to lower doses,but not to the highest dose, of acetylcholine was diminished, to sodium nitroprusside was increased, and to diazoxide was unaffected after L-NAME, compared to control conditions. The effects on cerebrovascular resistance to acetycholine normalized within 24 h and to sodium nitroprusside within 48 h after L-NAME treatment.6. This study provides information about the evolution of the changes in cerebral blood flow and cerebrovascular 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 resting vasodilator tone, (b) the cerebral vasodilatation to acetylcholine is mediated, at least in part, by nitric oxide release, and (c) inhibition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Fernández
authors.forename: J L
authors.initials: JL
authors.lastname: García
authors.forename: A L
authors.initials: AL
authors.lastname: García-Villalón
authors.forename: L
authors.initials: L
authors.lastname: Monge
authors.forename: B
authors.initials: B
authors.lastname: Gómez
authors.forename: G
authors.initials: G
authors.lastname: Diéguez
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D006339:Heart Rate / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D003981:Diazoxide; D019331:NG-Nitroarginine Methyl Ester