Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat.
Obesity causes whole body insulin resistance and impaired vasodilation to nitric oxide (NO). Because NO is a major contributor to the regulation of mesenteric blood flow, the mesenteric circulation of obese animals is faced with reduced capacity to increase flow and increased demand for flow associated with elevated consumption of food. This study hypothesized that insulin resistance impairs NO-mediated dilation but that constrictor reactivity would be reduced to compensate in obese animals. We further hypothesized that elevated superoxide levels caused impaired responses to NO in insulin resistance. Vasodilator reactivity and vasoconstrictor reactivity of mesenteric resistance arteries from lean (LZR) and obese (OZR) Zucker rats were examined in vitro using videomicroscopy. Insulin resistance independent of obesity was induced via fructose feeding in LZR (FF-LZR). Endothelium-dependent NO-mediated dilation was reduced in OZR and FF-LZR compared with LZR. Impairments in NO-mediated dilation were reversed with 1 mM tempol, a SOD mimetic. Constrictor reactivity to norepinephrine was reduced in OZR but not in FF-LZR relative to LZR. Basal mesenteric vascular resistance was similar in LZR and OZR despite impaired NO-dependent dilation in OZR. Mesenteric vascular resistance was increased in FF-LZR relative to LZR. These data indicate that there is reduced constrictor reactivity in OZR that may offset the impaired NO-mediated dilation and preserve mesenteric blood flow in hyperphagic, obese animals.
Romanko
Olga P
OP
Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta GA 30912, USA.
Stepp
David W
DW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013113:Spin Labels; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016232:Endothelins; D013113:Spin Labels; D013566:Sympathomimetics; D014665:Vasodilator Agents; D013481:Superoxides; D011189:Potassium Chloride; D000109:Acetylcholine; C001803:tempol; D009638:Norepinephrine