ENDOTHELIAL-DEPENDENT VASODILATION IS PRESERVED IN NON-INSULIN-DEPENDENT ZUCKER FATTY DIABETIC RATS

Alterations in the structural properties of the microvasculature and i n vasodilation mediated by endothelial- and, to some extent, nonendoth elial-dependent mechanisms occurs in insulin-dependent diabetic humans and animals. Less severe problems of this type appear to occur during non-insulin-dependent diabetes mellitus (NIDDM) in humans, but data b ased on animal models of NIDDM are not available. The endothelial- and nonendothelial-mediated dilation of intestinal arterioles was studied in insulin-resistant male Zucker fatty diabetic (DB) rats and their l ean normal male littermates (LM) at ages 22-25 and 35-40 wk. DB become hyperglycemic (450-550 mg/100 ml) at age 9-10 wk. Microiontophoretic release of acetylcholine, ADP, and nitroprusside onto arterioles cause d equivalent dilation in LM and DB for both large and intermediate dia meter arterioles. Administration of streptozotocin (STZ) to DB at age 18-19 wk lowered their insulin concentration similar to 25% but did no t significantly effect the resting plasma glucose concentration. Howev er, endothelial-dependent vasodilation was attenuated by 70-80% within 8-10 wk. The overall results indicate that prolonged hyperglycemia in insulin-resistant but hyperinsulinemic rats does not impair the endot helial- and nonendothelial-dependent dilation of the intestinal microv asculature. However, compromising beta-cell function with STZ, as indi cated by lowering the insulin concentration by one-fourth, substantial ly compromises endothelial-dependent dilation similar to that found in insulin-dependent diabetic rats and humans.