Non-insulin-dependent diabetes and hyperglycemia impair rat intestinal flow-mediated regulation.
Release of nitric oxide from small arteries and larger arterioles of the intestine maintains their dilation and thereby supports mucosal blood flow. This flow-dependent mechanism can be studied by isosmotic replacement of sodium chloride with mannitol over the mucosa to lower mucosal metabolism and blood flow requirements. We tested the hypothesis that flow-mediated regulation is impaired in the non-insulin-dependent Zucker fatty diabetic (ZFD) male rats because of their marginally impaired endothelium-dependent dilation. Furthermore, we determined whether the depressed acetylcholine dilation associated with acute hyperglycemia in normoglycemic Zucker (NZ) rats also impairs flow-mediated regulation. When mannitol replaced sodium chloride over the villi, intestinal blood flow decreased significantly (P < 0.05) less in ZFD (80.9 +/- 6.8% of control) than NZ rats (40.9 +/- 6.4% of control). After 300 mg/dl hyperglycemia for 30 min, normal arterioles had impaired responses to acetylcholine and the resting blood flow and oxygen consumption were suppressed about 60%, which indicate the importance of basal nitric oxide release for intestinal vascular support of metabolism. The evidence of impaired flow-mediated dilation in ZFD and decreased resting blood flow after hyperglycemia in NZ rats demonstrated that both acute and chronic hyperglycemia disturb endothelial regulation of the intestinal vasculature.
Jin
J S
JS
Department of Physiology and Biophysics, Indiana University Medical School, Indianapolis 46202, USA.
Bohlen
H G
HG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D006943:Hyperglycemia / Q000503:physiopathology*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009765:Obesity / Q000235:genetics; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D008353:Mannitol; D000109:Acetylcholine