Endothelin-1 and cerebral blood flow: Influence of hypoxia, hypercapnia and indomethacin on circulating endothelin levels in healthy volunteers

We investigated the effect of moderate (FiO2 13%) and light hypoxia (FiO2 17%) and hypercapnia (CO2 2-4%) with or without indomethacin on circulating levels of endothelin/endothelins (ET) and cerebral blood flow (CBF) in healthy volunteers. In protocol A, 23 subjects were exposed to moderate hypoxia. In protocol B, 29 subjects were randomized to one of four groups: (1) placebo, (2) indomethacin, (3) indomethacin + light hypoxia and (4) indomethacin + hypercapnia. Indomethacin was given as an intravenous bolus dose of 0.4mgkg−1 body weight followed by continuous infusion of 0.4mgkg−1h−1 for 6h. Two different FiO2 were chosen, light hypoxia in protocol B was chosen due to application of a known cerebral vasoconstrictor with unknown effect on cerebral autoregulation. We found, that moderate hypoxia (protocol A) induced a significant increase in CBF from 59.0 to 73.0ml 100 g−1 brain tissue min−1 (p < 0.00005) with an increase in circulating levels of ET from 1.7 to 1.9fmol ml−1 plasma. However, this differenc...