Role of endothelium-derived prostaglandins in hypoxia-elicited arteriolar dilation in rat skeletal muscle.

The aims of the present study were to determine the response of rat cremaster muscle first-order arterioles to hypoxia and the role of endothelium-derived prostaglandins in the response. Isolated arterioles were cannulated, pressurized to 65 mm Hg, and studied in a no-flow condition in a bath containing Krebs' bicarbonate solution, pH 7.4, equilibrated with 21% O2-5% CO2-74% N2 (PO2, 150 mm Hg) or 95% N2-5% CO2 (PO2, 15 mm Hg [hypoxia]). Responses to hypoxia and vasoactive substances were studied before and after removal of the endothelium or blockade of prostaglandin synthesis by the administration of indomethacin (10(-5) M). Addition to the suffusion solution of arachidonic acid (10(-7) and 10(-6) M), prostaglandin E2 (10(-9) and 10(-8) M), acetylcholine (10(-8) and 10(-6) M), or sodium nitroprusside (10(-8) M) evoked significant arteriolar dilation. When the bath PO2 was reduced from 150 to 15 mm Hg, arteriolar diameters increased by 58.8 +/- 9.3 microns (61%). Removal of the endothelium completely inhibited responses to hypoxia, acetylcholine, and arachidonic acid, whereas responses to sodium nitroprusside and prostaglandin E2 remained unaltered. In arterioles with an intact endothelium, indomethacin completely inhibited the responses to hypoxia and arachidonic acid, whereas responses to acetylcholine and sodium nitroprusside were unaltered. These findings support the conclusion that endothelium-derived prostaglandins mediate the arteriolar dilation to hypoxia in rat skeletal muscle arterioles.