Cerebral blood flow regulation in women across menstrual phase: differential contribution of cyclooxygenase to basal, hypoxic, and hypercapnic vascular tone.

In healthy young women, basal cerebral blood flow (CBF) and cerebrovascular reactivity may change across the menstrual cycle, but mechanisms remain untested. When compared with the early follicular phase of the menstrual cycle, we hypothesized women in late follicular phase would exhibit: 1) greater basal CBF, 2) greater hypercapnic increases in CBF, 3) greater hypoxic increases in CBF, and 4) increased cyclooxygenase (COX) signaling. We measured middle cerebral artery velocity (MCAv, transcranial Doppler ultrasound) in 11 healthy women (23 ± 1 yr) during rest, hypoxia, and hypercapnia. Subjects completed four visits: two during the early follicular (∼day 3) and two during the late follicular (∼day 14) phases of the menstrual cycle, with and without COX inhibition (oral indomethacin). Isocapnic hypoxia elicited an SPO2 = 90% and SPO2 = 80% for 5 min each. Separately, hypercapnia increased end-tidal CO2 10 mmHg above baseline. Cerebral vascular conductance index (CVCi = MCAv/MABP·100, where MABP is mean arterial blood pressure) was calculated and a positive change reflected vasodilation (ΔCVCi). Basal CVCi was greater in the late follicular phase (P < 0.001). Indomethacin decreased basal CVCi (∼37%) and abolished the phase difference (P < 0.001). Hypoxic ΔCVCi was similar between phases and unaffected by indomethacin. Hypercapnic ΔCVCi was similar between phases, and indomethacin decreased hypercapnic ΔCVCi (∼68%; P < 0.001) similarly between phases. In summary, while neither hypercapnic nor hypoxic vasodilation is altered by menstrual phase, increased basal CBF in the late follicular phase is fully explained by a greater contribution of COX. These data provide new mechanistic insight into anterior CBF regulation across menstrual phases and contribute to our understanding of CBF regulation in women.

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

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 (PETCO 2) 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.