Effects of streptozotocin-induced diabetes on vascular reactivity in genetically hyperinsulinaemic obese Zucker rats

Although the fa/fa Zucker rat shows many of the features of type II diabetes, the absence of consistent cardiovascular complications in this model may be due to the absence of significant hyperglycaemia. We studied the consequences of streptozotocin (STZ)-induced insulin deficiency and hyperglycaemia on vascular reactivity in the fa/fa Zucker rat. Hyperinsulinaemic obese Zucker rats were rendered diabetic by injection of STZ (50-60 mg/kg intraperitoneally, i.p.), and vascular tissue was removed for study 10-12 weeks later. In isolated aorta, there was no difference in the phenylephrine (PE) concentration-response relation between lean and obese control animals, but the concentration-response curve was shifted to the left in diabetic animals, (pD(2) 7.56 +/- 0.04 in STZ diabetic animals, n = 8; 7.4 +/- 0.04 in obese control, n = 9, p < 0.05); The maximum response was also enhanced in both aorta and perfused mesentery of STZ-treated animals. In contrast, the potency of serotonin (5-HT) in inducing contractions of isolated aorta were enhanced in tissues from obese as compared with lean animals (pD(2) 6.63 +/- 0.06, n = 9; 6.17 +/- 0.07, n = 7 respectively; p < 0.01) and was attenuated in animals with STZ-induced diabetes (pD(2) 6.31 +/- 0.09, n = 8, p = 0.05). The differential effects of hyperglycaemia on PE and 5-HT-induced vasoconstriction suggest that the long-lasting modulation of vasoconstrictor responses induced by increases in blood glucose level may be specific for some agonists.