Gender-related effects of indomethacin on cerebrovascular CO2 reactivity

Prostaglandins are believed to play an important role in the regulation of resting cerebral blood flow and in the vasodilatory response to hypercapnia. Recently, we reported an increased CO2 reactivity (CR) in premenopausal women and, in the past, evidence has accumulated that estrogens might increase basal levels of prostaglandin secretion from endothelial cells. Therefore, one may speculate that gender differences in CR are possibly mediated by higher prostaglandin levels in women. Using transcranial Doppler sonography, we assessed CR before and 90 min after a single dose of 100 mg of indomethacin in 22 healthy volunteers (11 men, 11 women). Before intake of indomethacin, women had a significantly higher CR (4.53+/-0.49 vs. 3.61+/-0.74, P<0.01). Ninety minutes after indomethacin administration, CR decreased to 1.53+/-0.93 in women and 1.60+/-0.92 in men, respectively. The change of CR was 3.00+/-1.29 in women vs. 2.01+/-1.06 in men (P=0.07). For the entire study population, the decrease of CR was linearly correlated with the initial value of CR (rs=0.74, P<0.001). This gender-related difference possibly relates to higher prostaglandin levels as mediators of an increased CR in premenopausal women, although the exact features remain to be clarified.