Advanced glycosylation end-products and NO-dependent vasodilation in renalafferent arterioles from diabetic rats

Systemic pressor responses to acetylcholine (ACh) are reduced in DM, an eff ect thought to be related to quenching of nitric oxide (NO) by advanced gly cosylation end-products (AGE). We studied the effects of AGE in juxtamedull ary (JM) afferent arterioles (AA) from rats with 40-50 days diabetes mellit us (DM) induced via streptozotocin. JM AA were perfused in vitro with solut ions containing fresh RBCs suspended in either 6% bovine albumin or 6% AGE- albumin in euglycaemic Krebs-Ringer. Autoregulatory responses were evident in the DM vessels: AA constricted 31 +/- 2% (n = 9) when perfusion pressure (PP) was raised from 60 to 140 mmHg. ACh (10 mu M) caused a 43 +/- 15% dil ation and Ca2+-channel blockade elicited a 95 +/- 14% dilation at 100 mmHg PP, indicating substantial basal vascular tone in DM AA. L-NAME (0.1 mM) co nstricted DM AA by 21 +/- 2% (n = 9) at 100 mmHg PP, indicating significant basal NO production in DM vessels. Segments of renal resistance arteries f rom DM rats perfused in vitro responded to muscarinic stimulation and eleva ted glucose levels with significant increments in NO production, as measure d with an NO-sensitive electrode. This observation shows that the renal end othelial NO system is intact in DM. While AGE in the perfusate dilated cont rol AA, they had no effect on DM AA at all PP levels, although they blunted ACh-induced dilation. Hence, although AGE do appear to have vasoactive pro perties in the absence of hyperglycaemia, the results of this study are inc onsistent with substantial NO quenching by AGE.