Electrical and mechanical responses of rat middle cerebral arteries to reduced P O 2 and prostacyclin

Abstract

Isolated rat middle cerebral arteries were perfused and superfused with physiological salt solution equilibrated with a control (∼140 mmHg) or reduced (∼35–40 mmHg)[Formula: see text]. In other experiments, cerebral arteries were isolated and prostacyclin release was determined by radioimmunoassay for 6-ketoprostaglandin F1α. Equilibration of the vessels with reduced[Formula: see text] (35 mmHg) solution caused a significant increase in prostacyclin release relative to control[Formula: see text] (140 mmHg) conditions. Exposure of middle cerebral arteries to reduced[Formula: see text] caused vascular smooth muscle (VSM) hyperpolarization and vessel relaxation, which could be blocked by 1 μM glibenclamide, an inhibitor of the ATP-sensitive K+ channel, but not by 1 mM tetraethylammonium (TEA), an inhibitor of the Ca2+-activated K+ channel. Glibenclamide also inhibited VSM hyperpolarization and vasodilation in response to the stable prostacyclin analog iloprost, but TEA did not affect iloprost-induced dilation of the vessel. Endothelial removal eliminated the electrical and mechanical responses of the arteries to reduced[Formula: see text], but vessel responses to iloprost were similar to those of intact vessels. The results of this study are consistent with the hypothesis that hypoxic dilation of rat middle cerebral arteries is due to VSM hyperpolarization mediated by prostacyclin-induced activation of glibenclamide-sensitive K+ channels.