LIFE SCIENCES, vol.68, no.5, pp.557-568, 2000 (SCI-Expanded)
Troglitazone, a thiazolidinedione derivative, is an oral antidiabetic agent that enhances insulin sensitivity in insulin-resistant states. K-ATP channels, on the other hand, have important roles protecting cardiovascular system in ischemic and for hypoxic states. They are also important in the control of vascular tone, and therefore of blood pressure. We tested whether troglitazone can directly affect vascular K-ATP channel opener-induced relaxations in vitro. 1, 10 or 100 muM troglitazone incubations for 30 min did not alter cromakalim (a K-ATP channel opener) - induced relaxations in endothelium-denuded aortas from rat, saphenous veins from type 2 diabetic and nondiabetic 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, pD(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 response of cromakalim was also significantly decreased by 24 +/- 3% in diabetic veins. However, responsiveness of veins to phenylephrine or sodium nitroprusside were similar in both groups. The results obtained may be clinically useful 1. suggesting that in ischaemic and I or hypoxic insults troglitazone may not worsen vascular dilatation, through K-ATP channel, in diabetic patients who are more prone to these conditions than healthy people, 2, providing an evidence that diabetes causes an impaired dilatation of human saphenous vein through K-ATP channels. This may partly be related with diabetes-induced vascular complications, such as vasospasm and even hypertension. Accordingly, 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 reserved.