Differential contribution of cyclooxygenase to basal cerebral blood flow and hypoxic cerebral vasodilation

Abstract

Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation ([Formula: see text])]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% ( P < 0.001) and artery CSA ( P < 0.001), which was similar across arteries. Hypoxia ([Formula: see text] 80%–83%) increased CVC ( P < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/−Δ[Formula: see text]) across arteries ( P < 0.05), in part because of increases in CSA ( P < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/Δ[Formula: see text] to hypoxia. These findings indicate that 1) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and 2) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries.