Alteration of vascular reactivity in diabetic human mammary artery and the effects of thiazolidinediones.
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 K(ATP)-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 microM) and rosiglitazone (1 and 20 microM), 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 microM, rosiglita-zone 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.
Irat
Ali Murat
AM
Department of Pharmacology, University of Ankara, Tandoğan 06100, Ankara, Turkey.
Aslamaci
Sait
S
Karasu
Cimen
C
Ari
Nuray
N
D000368:Aged; D019806:Cromakalim / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D000077205:Pioglitazone; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019806:Cromakalim; D009599:Nitroprusside; D010656:Phenylephrine; D011189:Potassium Chloride; D005905:Glyburide; D000077205:Pioglitazone