Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats.
This study characterized myogenic activation of skeletal muscle (gracilis) resistance arteries from lean (LZR) and obese Zucker rats (OZR). Arteries from OZR exhibited increased myogenic activation versus LZR; this increase was impaired by endothelium denudation or nitric oxde synthase inhibition. Treatment of vessels with 17-octadecynoic acid impaired responses in both strains by comparable amounts. Dihydroethidine microfluorography indicated elevated vascular superoxide levels in OZR versus LZR; immunohistochemistry demonstrated elevated vascular nitrotyrosine levels in OZR, indicating increased peroxynitrite presence. Vessel treatment with oxidative radical scavengers (polythylene glycol-superoxide dismutase/catalase) or inhibition of Ca(2+)-activated K(+) (K(Ca)) channels (iberiotoxin) did not alter myogenic activation in LZR but normalized activation in OZR. Application of peroxynitrite to vessels of OZR caused a greater vasoconstriction versus LZR; the response was impaired in OZR by elevated intraluminal pressure and was abolished in both strains by iberiotoxin. These results suggest that enhanced myogenic activation of gracilis arteries of OZR versus LZR 1) is not due to alterations in cytochrome P-450 contribution, and 2) may be due to elevated peroxynitrite levels inhibiting K(Ca) channels following increased intraluminal pressure.
Frisbee
Jefferson C
JC
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA. jfrisbee@mcw.edu
Maier
Kristopher G
KG
Stepp
David W
DW
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002374:Catalase / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000494:pharmacology / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors; D051381:Rats; D011924:Rats, Zucker; D013482:Superoxide Dismutase / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology
D005231:Fatty Acids, Unsaturated; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D030421:Peroxynitrous Acid; C047008:17-octadecynoic acid; C002744:3-nitrotyrosine; D011092:Polyethylene Glycols; D014443:Tyrosine; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase