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


Irat A. M. , Aslamaci S., Karasu C., Ari N.

JOURNAL OF PHARMACY AND PHARMACOLOGY, vol.58, no.12, pp.1647-1653, 2006 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 58 Issue: 12
  • Publication Date: 2006
  • Doi Number: 10.1211/jpp.58.12.0012
  • Title of Journal : JOURNAL OF PHARMACY AND PHARMACOLOGY
  • Page Numbers: pp.1647-1653

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 mu m)and rosiglitazone (1 and 20 mu m), for 30 min, did not affect K-ATP-channel-mediated relaxations (n = 5 each, P > 0.05). Pioglitazone partly inhibited pre-contractions of PE and KCl at 10 mu m, 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 K-ATP channels in ischaemic or hypoxic insults in diabetic patients who are prone to such conditions. Pioglitazone has vasorelaxant property in the grafts.