Impaired NO-dependent dilation of skeletal muscle arterioles in hypertensive diabetic obese Zucker rats.
This study determined alterations to nitric oxide (NO)-dependent dilation of skeletal muscle arterioles from obese (OZR) versus lean Zucker rats (LZR). In situ cremaster muscle arterioles from both groups were viewed via television microscopy, and vessel dilation was measured with a video micrometer. Arteriolar dilation to acetylcholine and sodium nitroprusside was reduced in OZR versus LZR, although dilation to aprikalim was unaltered. NO-dependent flow-induced arteriolar dilation (via parallel microvessel occlusion) was attenuated in OZR, impairing arteriolar ability to regulate wall shear rate. Vascular superoxide levels, as assessed by dihydroethidine fluorescence, were elevated in OZR versus LZR. Treatment of cremaster muscles of OZR with the superoxide scavengers polyethylene glycol-superoxide dismutase and catalase improved arteriolar dilation to acetylcholine and sodium nitroprusside and restored flow-induced dilation and microvascular ability to regulate wall shear rate. These results suggest that NO-dependent dilation of skeletal muscle microvessels in OZR is impaired due to increased levels of superoxide. Taken together, these data suggest that the development of diabetes and hypertension in OZR may be associated with an impaired skeletal muscle perfusion via an elevated vascular oxidant stress.
Frisbee
J C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. jfrisbee@mcw.edu
Stepp
D W
DW
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology*; D002374:Catalase / Q000494:pharmacology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity; D018384:Oxidative Stress; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013314:Stress, Mechanical; D013482:Superoxide Dismutase / Q000494:pharmacology; D013851:Thinness / Q000150:complications / Q000503:physiopathology; D014654:Vascular Patency / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011092:Polyethylene Glycols; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase