NON-INSULIN-DEPENDENT DIABETES AND HYPERGLYCEMIA IMPAIR RAT INTESTINAL FLOW-MEDIATED REGULATION

Release of nitric oxide from small arteries and larger arterioles of t he intestine maintains their dilation and thereby supports mucosal blo od flow. This flow-dependent mechanism can be studied by isosmotic rep lacement of sodium chloride with mannitol over the mucosa to lower muc osal 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 imp aired endothelium-dependent dilation. Furthermore, we determined wheth er the depressed acetylcholine dilation associated with acute hypergly cemia in normoglycemic Zucker (NZ) rats also impairs flow-mediated reg ulation. When mannitol replaced sodium chloride over the villi, intest inal 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 respon ses to acetylcholine and the resting blood flow and oxygen consumption were suppressed about 60%, which indicate the importance of basal nit ric oxide release for intestinal vascular support of metabolism. The e vidence of impaired flow-mediated dilation in ZFD and decreased restin g blood flow after hyperglycemia in NZ rats demonstrated that both acu te and chronic hyperglycemia disturb endothelial regulation of the int estinal vasculature.