The goal of this study was to determine the effect of angiotensin AT₁ receptor antagonism on vasodilator responses in isolated skeletal muscle resistance arteries. Normotensive Sprague-Dawley rats were fed normal rat chow with the AT₁ receptor antagonist losartan (1mg/ml) in the drinking water for 7 days and compared to untreated control rats. Changes in the diameter of isolated resistance arteries supplying the gracilis muscle were assessed with a video micrometer. Arteriolar responses to acetylcholine, iloprost, and sodium nitroprusside were unaffected by losartan administration, while dilation to reduced PO₂ was converted into a constriction. Hypoxia-induced constriction of vessels from losartan-treated rats was inhibited by endothelium removal or indomethacin (1 µM). Blockade of the PGH₂/TXA₂ receptor with SQ-29548 (10 µM), thromboxane synthase inhibition with dazoxiben (10 µM), or addition of the superoxide dismutase mimetic tempol (100 µM) converted hypoxic vasoconstriction to a dilation that was blocked by inhibiting NOS with L-NAME (100 µM). These data suggest that AT₁ receptor activation has an important role in maintaining the vascular release of prostaglandins responsible for mediating hypoxic dilation in skeletal muscle microvessels. endothelium; microcirculation