High glucose concentration augments angiotensin II mediated contraction via AT1 receptors in rat thoracic aorta

Elevated glucose concentration is implicated to play major role in development of diabetic associated vascular complications. It was previously reported that angiotensin II (Ang 11) induced contractile response is enhanced in thoracic aorta of diabetic rats. In the present study, the effect of high glucose (HG, 25 mM) exposure for 2 h on Ang 11 cumulative concentration response curves recorded isometrically was studied in thoracic aortic rings isolated from male Sprague-Dawley rats pretreated with streptozotocin (STZ, 65 mg kg(-1) i.p.) or vehicle at 8 weeks prior to the study. Ang II induced contraction via AT I receptor was significantly enhanced (by 60 2%) in HG exposed thoracic aortic rings isolated from vehicle treated but not STZ treated rats. However, there was no change in the pD(2)) of Ang 11 while potassium chloride (KCl) induced contraction was unaltered. Ang 11 induced contractile response was blocked by valsartan (100 muM, selective AT, receptor antagonist) but not PD 123,319 (100 muM, selective and potent AT(2)) receptor antagonist). Exposure of aortic rings from control rats to 25 mM mannitol or sucrose for 2 h did not have any effect on the Ang 11 induced contraction. Tempol (100 muM, a cell permeable superoxide dismutase mimetic) partially reduced the augmented Ang 11 response in HG exposed aortic rings, while it did not affect the Ang H responses in normal glucose (NG 5.5 mM) exposed aortic rings isolated from control rats. [H-3] Ang 11 binding at AT, receptors was unaltered in vascular smooth muscle membranes prepared from thoracic aorta exposed to HG for 2 It compared to NG exposed aortic rings. From our results, we conclude that high glucose concentration augments Ang 11 mediated contraction via AT, receptors and reactive oxygen species partly contribute to this augmented contraction. (C) 2004 Elsevier Ltd. All rights reserved.