Endothelial function in the isolated perfused mesentery and aortae of rats with streptozotocin‐induced diabetes: effect of treatment with the aldose reductase inhibitor, ponalrestat

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Abstract
1 Noradrenaline sensitivity and relaxation to acetylcholine were investigated in the isolated perfused mesentery and in aortic rings of control and streptozotocin (STZ)-induced (50 mg kg−1) diabetic Charles River 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 reductase inhibitor, ponalrestat (100 mg kg−1 day−1). 3 The untreated diabetic rats (2–10 weeks after injection of STZ) demonstrated enhanced vascular sensitivity to noradrenaline in the perfused mesenteric arterial tree, compared with age matched controls (pEC50 [-log concentration (M)]: diabetic 5.62 ± 0.09, n = 18, versus control 5.23 ± 0.07, n = 16, P < 0.01). 4 Acetylcholine-induced relaxation was significantly impaired in the perfused mesentery of the diabetic animals compared to controls (pED50 [- 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 differences between the diabetic and control groups in response to either noradrenaline (pEC50: diabetic 7.66 ± 0.08, n = 15, versus controls 7.55 ± 0.06, n = 15, NS), or acetylcholine (pEC50: diabetics 7.30 ± 0.06, n = 15, versus controls 7.40 ± 0.09, n = 15, NS). 6 Treatment with the aldose reductase inhibitor, ponalrestat, did not affect the increased vascular reactivity to noradrenaline, or impaired relaxation to acetylcholine in the perfused mesentery.