Electrical and mechanical responses of rat middle cerebral arteries to reduced Po-2 and prostacyclin

Isolated rat middle cerebral arteries were perfused and superfused with phy siological salt solution equilibrated with a control (similar to 140 mmHg) or reduced (similar to 35-40 mmHg) PO2. In other experiments, cerebral arte ries were isolated and prostacyclin release was determined by radioimmunoas say for 6-ketoprostaglandin F-1 alpha. Equilibration of the vessels with re duced PO2 (35 mmHg) solution caused a significant increase in prostacyclin release relative to control PO2 (140 mmHg) conditions. Exposure of middle c erebral arteries to reduced PO2 caused vascular smooth muscle (VSM) hyperpo larization and vessel relaxation, which could be blocked by 1 mu M glibencl amide, an inhibitor of the ATP-sensitive K+ channel, but not by 1 mM tetrae thylammonium (TEA), an inhibitor of the Ca2+-activated K+ channel. Glibencl amide also inhibited VSM hyperpolarization and vasodilation in response to the stable prostacyclin analog iloprost, but TEA did not affect iloprost-in duced dilation of the vessel. Endothelial removal eliminated the electrical and mechanical responses of the arteries to reduced PO2, but vessel respon ses to iloprost were similar to those of intact vessels. The results of thi s study are consistent with the hypothesis that hypoxic dilation of rat mid dle cerebral arteries is due to VSM hyperpolarization mediated by prostacyc lin-induced activation of glibenclamide-sensitive K+ channels.