Troglitazone has no effect on K-ATP channel opener induced-relaxations in rat aorta and in human saphenous veins from patients with type 2 diabetes

Troglitazone, a thiazolidinedione derivative, is an oral antidiabetic agent that enhances insulin sensitivity in insulin-resistant states. K-ATP chann els, on the other hand, have important roles protecting cardiovascular syst em in ischemic and for hypoxic states. They are also important in the contr ol of vascular tone, and therefore of blood pressure. We tested whether tro glitazone can directly affect vascular K-ATP channel opener-induced relaxat ions in vitro. 1, 10 or 100 muM troglitazone incubations for 30 min did not alter cromakalim (a K-ATP channel opener) - induced relaxations in endothe lium-denuded aortas from rat, saphenous veins from type 2 diabetic and nond iabetic patients. In addition, we compared the sensitivity to cromakalim in diabetic saphenous veins with that of nondiabetic veins. The concentration -response curve for cromakalim was shifted to the right in diabetic vein, p D(2) values for cromakalim were 6.85 +/- 0.08 vs. 6.61 +/- 0.04 (p<0.05) in nondiabetic (n:10) and diabetic (n:7) veins respectively. % maximum respon se of cromakalim was also significantly decreased by 24 +/- 3% in diabetic veins. However, responsiveness of veins to phenylephrine or sodium nitropru sside were similar in both groups. The results obtained may be clinically u seful 1. suggesting that in ischaemic and I or hypoxic insults troglitazone may not worsen vascular dilatation, through K-ATP channel, in diabetic pat ients who are more prone to these conditions than healthy people, 2, provid ing an evidence that diabetes causes an impaired dilatation of human saphen ous vein through K-ATP channels. This may partly be related with diabetes-i nduced vascular complications, such as vasospasm and even hypertension. Acc ordingly, since saphenous veins are used as conduit vessels in coronary by- pass graft surgery, the results also suggest that the defective dilatation through K-ATP channels may pray a role on the performance of saphenous vein grafts in type 2 diabetes. (C) 2000 Elsevier Science Inc. All rights reser ved.