Electrical and mechanical responses of rat middle cerebral arteries to reduced PO2 and prostacyclin.

Abstract

Isolated rat middle cerebral arteries were perfused and superfused with physiological salt solution equilibrated with a control (approximately 140 mmHg) or reduced (approximately 35-40 mmHg) PO2. In other experiments, cerebral arteries were isolated and prostacyclin release was determined by radioimmunoassay for 6-ketoprostaglandin F1alpha. Equilibration of the vessels with reduced PO2 (35 mmHg) solution caused a significant increase in prostacyclin release relative to control PO2 (140 mmHg) conditions. Exposure of middle cerebral arteries to reduced PO2 caused vascular smooth muscle (VSM) hyperpolarization and vessel relaxation, which could be blocked by 1 microM 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 PO2, 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.