Impaired dilation of skeletal muscle microvessels to reduced oxygen tension in diabetic obese Zucker rats

This study determined alterations to hypoxic dilation of isolated skeletal muscle resistance arteries (gracilis arteries; viewed via television micros copy) from obese Zucker rats (OZR) compared with lean Zucker rats (LZR). Hy poxic dilation was reduced in OZR compared with LZR. Endothelium removal an d cyclooxygenase inhibition (indomethacin) severely reduced this response i n both groups, although nitric oxide synthase inhibition (NO-nitro-L-argini ne methyl ester) reduced dilation in LZR only. Treatment of vessels with a PGH(2)-thromboxane A(2) receptor antagonist had no effect on hypoxic dilati on in either group. Arterial dilation to arachidonic acid, iloprost, acetyl choline, and sodium nitroprusside was reduced in OZR versus LZR, although d ilation to forskolin and aprikalim was unaltered. Treatment of arteries fro m OZR with oxidative radical scavengers increased dilation to hypoxia and a gonists, with no effect on responses in LZR. The restored hypoxic dilation in OZR was abolished by indomethacin. These results suggest that hypoxic di lation of skeletal muscle microvessels from LZR represents the summated eff ects of prostanoid. and nitric oxide release, whereas the impaired response of vessels in OZR may reflect scavenging of PGI(2) by superoxide anion.