Alteration of vascular reactivity in diabetic human mammary artery and the effects of thiazolidinediones

Authors


Professor of Pharmacology, Ankara University, Faculty of Pharmacy, Department of Pharmacology, Tandogan 06100 Ankara, Turkey. E-mail: ari@pharmacy.ankara.edu.tr

Abstract

Vascular reactivity was investigated in endothelium-denuded human internal mammary artery (IMA) rings from type 2 diabetic patients. It was also investigated whether insulin sensitizer thiazolidinedione drugs, pioglitazone and rosiglitazone, can directly affect the reactivity of IMA. Using organ bath techniques, cumulative concentration-response curves to phenylephrine (PE), KCl, cromakalim (CRO) and sodium nitroprusside (SNP) were constructed in diabetic and non-diabetic IMA rings. Means of maximal responses (% Emax) and pEC50 values (sensitivity) were compared. Emax values and the sensitivity to PE and KCl were increased while KATP-channel-mediated relaxations were reduced significantly in diabetic rings compared with non-diabetic rings (n = 5–12, P < 0.05). No changes were observed for SNP responses (n = 5, P > 0.05). Incubations with pioglitazone (1 and 10 μM) and rosiglitazone (1 and 20 μM), for 30 min, did not affect KATP-channel-mediated relaxations (n = 5 each, P > 0.05). Pioglitazone partly inhibited pre-contractions of PE and KCl at 10 μM, rosiglitazone did not. Vascular dysfunction observed in diabetic IMA may be of specific importance since they are widely used as coronary bypass material. Thiazolidinedione drugs may not worsen arterial dilatation through KATP channels in ischaemic or hypoxic insults in diabetic patients who are prone to such conditions. Pioglitazone has vasorelaxant property in the grafts.

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