Flow-induced dilatation in isolated resistance arteries from control and streptozotocin-diabetic rats

Abstract

Acetylcholine-induced vasodilatation is impaired in animal models of insulin-dependent diabetes mellitus (IDDM), and may result from altered nitric oxide synthesis or release. The response to intraluminal flow, a more physiologically relevant stimulus for nitric oxide release, is unknown. This study examined flow-induced responses in isolated resistance arteries from male Sprague-Dawley control and streptozotocin-diabetic (45 mg/kg i.v, 4 week duration) rats. Mesenteric arteries (4-5th order) were dissected and cannulated on a pressure myograph (mean internal diameter ± SEM at 40 mmHg, control 223 ± 8, n = 9 vs diabetic 239 ±12 μm, n = 8, NS). Arteries were preconstricted with noradrenaline (1 μmol/l) and intraluminal pressure raised and maintained at 80 mmHg. Luminal flow was raised in incremental steps (0-1.27 μl/s). Arteries from control animals dilated to flow while arteries from diabetic animals constricted (% change in internal diameter ± SEM at 0.79 μl/s: control 13.46 ± 6.52, n = 9 vs diabetic -7.44 ± 3.38%, n = 8; p < 0.005). Incubation with Nω-nitro-L-arginine methyl ester (0.1 mmol/l) abolished flow responses in arteries from controls but not from diabetic rats. In conclusion, impaired flow-induced nitric oxide-mediated vasodilatation may contribute to vascular disease in IDDM.