Hypercapnia induces dilation of large cerebral arteries and is mediated via a non‐selective cyclooxygenase pathway (LB704)

Abstract

Dogma in human physiology posits that hypercapnia induces arteriolar vasodilation, with little to no vasomotion in large cerebral arteries. Assuming that the middle cerebral artery (MCA) diameter remains unchanged during hypercapnia has validated use of transcranial Doppler ultrasound (TCD) as a surrogate measure of cerebral blood flow. We hypothesized that dilation of the internal carotid artery (ICA) would occur with hypercapnia and be mediated, in part, via a cyclooxygenase pathway. Moreover, we reasoned that MCA velocity (MCAv) reactivity would underestimate ICA flow reactivity. Before and 90 min following oral indomethacin (INDO; 1.45±0.2 mg/kg; mean ± SD), concurrent vascular ultrasound measures of beat‐to‐beat flow, diameter, and velocity through the ICA, and blood velocity in the downstream MCA (n=7) were made at rest and during incremental steady‐state hyperoxic (300mmHg PETO2) hypercapnia (+3, +6, and +9 mmHg PETCO2). The reactivity of ICA flow to hypercapnia (8.2±1.8 %/mmHg) was greater (P<0.01) than the velocity reactivity in the ICA and MCA (5.5±2.5 vs. 4.4±1.3%/mmHg, respectively; P=0.13). This discrepancy between flow and velocity reactivity was explained by a progressive dilation in ICA diameter with hypercapnia (1.0±0.5 %/mmHg). Following INDO, the slope of ICA dilation was reduced by 41.50% (P<0.05). The significance of these findings are: 1) the underestimation of MCAv reactivity compared to ICA flow reactivity suggests that the MCA dilates in response to hypercapnia: and 2) ~40% of hypercapnic ICA dilation is mediated by a non‐selective cyclooxygenase pathway.Grant Funding Source: Supported by the Natural Sciences and Engineering Research Council of Canada