ENDOTHELIAL FUNCTION IN THE ISOLATED-PERFUSED MESENTERY AND AORTAE OFRATS WITH STREPTOZOTOCIN-INDUCED DIABETES - EFFECT OF TREATMENT WITH THE ALDOSE REDUCTASE INHIBITOR, PONALRESTAT

1 Noradrenaline sensitivity and relaxation to acetylcholine were inves tigated in the isolated perfused mesentery and in aortic rings of cont rol and streptozotocin (STZ)-induced (50 mg kg(-1)) diabetic Charles R iver rats. 2 In addition, noradrenaline sensitivity and acetylcholine relaxation were similarly assessed in streptozotocin-induced diabetic rats treated from the time of onset of diabetes with the aldose reduct ase inhibitor, ponalrestat (100 mg kg(-1) day(-1)). 3 The untreated di abetic rats (2-10 weeks after injection of STZ) demonstrated enhanced vascular sensitivity to noradrenaline in the perfused mesenteric arter ial tree, compared with age matched controls (pECS(50) [- log concentr ation (M)]: diabetic 5.62 +/- 0.09, n = 18, versus control 5.23 +/- 0. 07, n = 16, P<0.01). 4 Acetylcholine-induced relaxation was significan tly impaired in the perfused mesentery of the diabetic animals compare d to controls (pEDS(50) [- log dose (mol)]: diabetic 9.87 +/- 0.10, n = 20, versus controls, 10.29 +/- 0.09, n = 20, P<0.05). 5 In contrast, the aortic ring preparations demonstrated no significant functional d ifferences between the diabetic and control groups in response to eith er noradrenaline (pEC(50): diabetic 7.66 +/- 0.08, n = 15, versus cont rols 7.55 +/- 0.06, n = 15, NS), or acetylcholine (pEC(50): controls 7 .40 +/- 0.09, n = 15, NS). 6 Treatment with the aldose reductase inhib itor, ponalrestat, did not affect the increased vascular reactivity to noradrenaline, or impaired relaxation to acetylcholine in the perfuse d mesentery.