Role of cyclooxygenase in sex‐specific cerebrovascular responses to hypoxia (708.2)

Abstract

Animal data suggest females rely more on cyclooxygenase (COX) than males to achieve increases in cerebral blood flow. Our aim was to determine the contribution of COX to hypoxia‐mediated increases in cerebral blood flow in young, healthy female and male humans. We hypothesized females would exhibit greater hypoxia‐mediated increases in cerebral blood flow due to increased COX signaling. We measured middle cerebral artery velocity (MCAv) with transcranial Doppler ultrasound in young (24±1 yr) females (n=12) and males (n=17). Females were studied during early follicular phase (cycle day 1 ‐ 5) to minimize the effects of female hormones. Inspired air was titrated to lower arterial O2 saturation to 80% for 5 minutes while end‐tidal CO2 was maintained at basal levels. MCAv was normalized for blood pressure as cerebrovascular conductance index (CVCi). Hypoxia was conducted on twice after ingestion of placebo or COX inhibitor (100mg indomethacin). Hypoxia increased CVCi (ΔCVCi) but ΔCVCi was not different between groups (females: 13±2 vs. males: 10±2 cm/s/mmHg, p=0.55). Indomethacin reduced ΔCVCi 4±3 cm/s/mmHg in females and increased ΔCVCi 0.5±2 cm/s/mmHg in males; however, the indomethacin‐mediated change in ΔCVCi was not statistically significant (p=0.15). Our data indicate males and females respond similarly to hypoxia, but COX may play a relatively larger role in females to mediate cerebral vasodilation. Grant Funding Source: AHA PRE7390038 & NIH HL105820