Recovery of microvascular responses during streptozotocin-induced diabetes

Microvascular reactivity of cannulated and pressurised rat cremaster arterioles was studied during the progress of diabetes using mechanical (intraluminal pressure) and chemical (acetylcholine, sodium nitroprusside) stimulation. Microvessels were studied in controls and at 2, 4 and 8 weeks following induction of diabetes by streptozotocin. Mechanical responses were stable at the test pressure (70 mmHg) used for pharmacological investigations during the period of diabetes. Acetylcholine application could induce maximal dilatation in control vessels and in vessels exposed to 8 weeks of diabetes. However, acetylcholine administration failed to generate maximal dilatation at 2 and 4 weeks of diabetes. During the period of diabetes, loss of nitric oxide (NO) pathway effectiveness was revealed by diminished response to sodium nitroprusside and by reduced capacity of Nomega-nitro-L-arginine methyl ester (L-NAME) to decrease resting diameter and acetylcholine-evoked dilatation. L-NAME and indomethacin application revealed a significant non-NO, non-prostaglandin contribution to the acetylcholine response at 4 and 8 weeks of diabetes. Recovery of responsiveness to acetylcholine and stabilisation of resting vessel diameter during diabetes may, in part, be due to increasing effectiveness of non-NO, non-prostaglandin pathways.