Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric oxide function.
Obesity is a risk for type II diabetes mellitus and increased vascular resistance. Disturbances of nitric oxide (NO) physiology occur in both obese animals and humans. In obese Zucker rats, we determined whether a protein kinase C-beta II (PKC-beta II) mechanism may lower the resting NO concentration ([NO]) and predispose endothelial NO abnormalities at lower glucose concentrations than occur in lean rats. NO was measured with microelectrodes touching in vivo intestinal arterioles. At rest, the [NO] in obese Zucker rats was 60 nm less than normal or about a 15% decline. After local blockade of PKC-beta II with LY-333531, the [NO] increased approximately 90 nm in obese rats but did not change in lean rats. In lean rats, administration of 300 mg/dl D-glucose for 45 min depressed endothelium-dependent dilation; only 200 mg/dl was required in obese animals. These various observations indicate that resting [NO] is depressed in obese rats by a PKC-beta II mechanism and the hyperglycemic threshold for endothelial NO suppression is reduced to 200 mg/dl D-glucose.
Bohlen
H G
HG
Department of Cellular and Integrative Physiology, Indiana University Medical School, Indianapolis, Indiana 46202, USA. gbohlen@iupui.edu
Nase
Geoffrey P
GP
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage; D006943:Hyperglycemia / Q000378:metabolism*; D007322:Instillation, Drug; D007333:Insulin Resistance / Q000502:physiology; D007421:Intestine, Small / Q000098:blood supply; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008839:Microelectrodes; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D064546:Protein Kinase C beta; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D005947:Glucose; D001920:Bradykinin