Effects of rosiglitazone and/or insulin on the vasoconstrictor and vasodilator responses of the thoracic aorta isolated from streptozotocin-induced diabetic rats

Dr. Ogulener, Nuran1, Dr. Bashan, Perihan1, Dr. Kavak, Servet2, Yorulmaz Ozu, Ozlem1, Dr. Secilmis, Ata1, Dr. Emre, Mustafa2. 1Cukurova University, Medical Faculty Pharmacology Department, Balcali, 01330 Adana, Turkey ; 2Cukurova University, Medical Faculty Biophysics Department, Balcali, 01330 Adana, Turkey.

Rosiglitazone, a thiazolidinedione, acts by improving glycaemic control and insulin sensitivity. In addition to their insulin-sensitizing action, glitazones also have antihypertensive effects. In this study, we aimed to investigate the effects of rosiglitazone and insulin on impaired vascular function in diabetes. For this purpose, we measured the isometric responses of aortic segments obtained from streptozotocin (STZ)-induced diabetic rats. To determine the effects of diabetes and test agents on the contractility of the vascular smooth muscle, a dose response curve was performed by phenylephrine and KCl. In order to determine endothelium dependent vasodilator responses, acetylcholine (Ach) was applied cumulatively to the organ bath. The contractile responses to KCl were markedly diminished in diabetic group and insulin aggravated this impairment. However, rosiglitazone restored the diminished contractile responses in diabetic group. Concentration-dependent responses to phenylephrine were significantly decreased in diabetic group and neither rosiglitazone nor insulin affected the decreased contractile responses in diabetic group. The relaxation responses to Ach in diabetic group were significantly weaker than the control group. Insulin but not rosiglitazone, restored the responses.

These findings suggest a) that both KCl and phe-induced contractile responses and Ach-induced vasodilator responses were impaired in the thoracic aorta isolated from the STZ-induced diabetic rats b) that insulin treatment restored the Ach-induced relaxant while aggravating the contractile responses c) that rosiglitazone treatment reversed the KCl-induced contractions but did affect neither phenylephrine nor Ach-induced responses.