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) 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.
Yöntem
O
O
Department of Pharmacology, Faculty of Pharmacy, University of Ankara, Turkey.
Sahilli
M
M
Karasu
C
C
Ozçelikay
A T
AT
Altan
V M
VM
Ari
N
N
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D002839:Chromans; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013844:Thiazoles; D045162:Thiazolidinediones; D019806:Cromakalim; D009599:Nitroprusside; D000077288:Troglitazone