# Cerebrovascular regulation in men and women: stimulus-specific role of cyclooxygenase

## TL;DR

This study found that women have higher baseline cerebral blood flow than men, but similar vasodilation responses to hypoxia and hypercapnia, with COX playing a key role in regulating blood flow in both sexes.

## Contribution

The study reveals sex-specific roles of COX in cerebral blood flow regulation during hypoxia and hypercapnia in humans.

## Key findings

- Women had greater baseline cerebral blood flow than men.
- COX inhibition reduced baseline and hypercapnic cerebral blood flow similarly in both sexes.
- COX is not essential for hypoxic vasodilation but is crucial for hypercapnic responses.

## Abstract

Greater cerebral artery vasodilation mediated by cyclooxygenase (COX) in female animals is unexplored in humans. We hypothesized that young, healthy women would exhibit greater basal cerebral blood flow (CBF) and greater vasodilation during hypoxia or hypercapnia compared to men, mediated by a larger contribution of COX. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 42 adults (24 women, 18 men; 24 ± 1 years) during two visits, in a double-blind, placebo-controlled design (COX inhibition, 100 mg oral indomethacin, Indo). Women were studied early in the follicular phase of the menstrual cycle (days 1–5). Two levels of isocapnic hypoxia (SPO2 = 90% and 80%) were induced for 5-min each. Separately, hypercapnia was induced by increasing end-tidal carbon dioxide (PETCO2) 10 mmHg above baseline. A positive change in MCAv (ΔMCAv) reflected vasodilation. Basal MCAv was greater in women compared to men (P < 0.01) across all conditions. Indo decreased baseline MCAv (P < 0.01) similarly between sexes. Hypoxia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo did not alter hypoxic vasodilation in either sex. Hypercapnia increased MCAv (P < 0.01), but ΔMCAv was not different between sexes. Indo elicited a large decrease in hypercapnic vasodilation (P < 0.01) that was similar between sexes. During the early follicular phase, women exhibit greater basal CBF than men, but similar vasodilatory responses to hypoxia and hypercapnia. Moreover, COX is not obligatory for hypoxic vasodilation, but plays a vital and similar role in the regulation of basal CBF (∼30%) and hypercapnic response (∼55%) between sexes.