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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/or 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 microM 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. pD2 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/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 play a role on the performance of saphenous vein grafts in type 2 diabetes.

The effects of non-insulin-dependent diabetes mellitus (NIDDM) were investigated on the reactivity of human internal mammary artery (IMA) and saphenous vein (SV) rings obtained from coronary artery patients (CAP) undergoing coronary artery bypass surgery. In the presence of endothelium, the maximal contractile response and sensitivity (pD2) of IMA or SV to NA and ET-1 significantly increased in CAP with NIDDM relative to CAP only (controls). Removal of the endothelium markedly and significantly enhanced the maximal contractile response and sensitivity of IMA or SV to NA in CAP only, but did not induce a significant alteration in CAP with NIDDM compared to that in the presence of endothelium. The maximal contractile response and sensitivity of diabetic vessels with or without endothelium to NA were similar to values of corresponding vessels without endothelium obtained from nondiabetic CAP. The maximum contractions developed by NA or ET-1 were much greater in SV than that determinated in the IMA. Acetylcholine (ACh) and histamine produced endothelium-dependent relaxations in precontracted IMA and these effects of ACh and histamine significantly decreased in CAP with NIDDM. Endothelium-dependent relaxations stimulated by ACh were more pronounced in IMA than that determinated in the SV. In precontracted SV, histamine induced marked contractions that were significantly greater in CAP with NIDDM relative to CAP only. Endothelium-independent relaxations of vessels to sodium nitroprusside (SNP) were not influenced by NIDDM. Data indicate that NIDDM causes a deficit in the vasorelaxant activity of endothelium, leading to an increase in contractility of human IMA and SV. Data also suggest that IMA can be a better choice of graft for coronary occlusive disease than SV, specially in patients with NIDDM.

Diabetes mellitus is known to produce alterations in vascular reactivity. In the present study we have examined the effects of endothelium-dependent and endothelium-independent relaxing substances on thoracic aorta from insulin-dependent (Type-1) and noninsulin-dependent (Type-2) diabetic rats and their appropriate controls. Endothelium-dependent relaxations produced by acetylcholine and histamine in aortic rings precontracted with noradrenaline were significantly increased in insulin-dependent diabetic vessels. In contrast, the relaxations elicited by those agents were significantly attenuated in noninsulin-dependent diabetic aorta preparations. On the other hand, the relaxations induced by sodium nitroprusside (an endothelium-independent relaxant agent) in both types of diabetic preparations were comparable to those in control vessels. The results indicate that insulin-dependent and noninsulin-dependent diabetes lead to specific alterations of the endothelium-dependent relaxation of rat aorta.