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 N0-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-' 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-' 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-' by i.v. bolus).4 Acetylcholine (0.01-0.3pg), sodium nitroprusside (3-100 g) and diazoxide (0.3-9mg), 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 lOO1ig) 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.

Endogenous Nitric Oxide Synthesis Differentially Modulates Pressure-Flow and Pressure-Conductance Relationships in the Internal and External Carotid Artery Circulations of the Rat

“…25,35) Consistent with previous reports in the rat and other species, 5,6,25) we also found that L-NMMA induced secondary bradycardia of approximately 30 bpm which is known to involve autonomic reflexes as it is abolished, and the associated pressor response potentiated, by baroreceptor deafferentiation. 35) In the present study, these systemic responses to L-NMMA were attenuated by pre-and post-administration of L-arginine, and changes in the P-Q characteristics of the ECA territory induced by L-NMMA were reversed by post-administration of L-arginine.…”

Nitrergic nerves derived from the pterygopalatine ganglion innervate arteries irrigating the cerebrum but not the cerebellum and brain stem in monkeys

“…[23][24][25][26][27] It is postulated that vasoconstriction is partially mediated by the suppression of NO, synthesized from L-arginine in the perivascular nerve terminals innervating the arteries that irrigate the cerebrum, as treatment with a ganglion blocker can suppress vasoconstriction or cause a decrease in blood flow. 21 We therefore conclude that in the arteries irrigating the cerebrum, cerebellum and brain stem, constrictions induced by intravenous L-NA may be partially associated with the suppression of nitrergic function.…”

A Large Blood Pressure–Raising Effect of Nitric Oxide Synthase Inhibition in Humans

“…[1][2][3][4][5][6] Although this experimental NOdeficient hypertension at first was attributed solely to inhibition of endothelium-dependent vasodilation, 1,7 there is increasing evidence of an important sympathetic neural component. 5,6,8 -12 The concept is that neuronally produced NO is part of the signal transduction pathway involved in the restraint of brainstem sympathetic vasomotor outflow and that inhibition of such restraint leads to neurogenic hypertension.…”