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 II) 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 2h on Ang II 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 AT1 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 pD2 of Ang II while potassium chloride (KCl) induced contraction was unaltered. Ang II induced contractile response was blocked by valsartan (100 microM, selective AT1 receptor antagonist) but not PD 123,319 (100 microM, selective and potent AT2 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 II induced contraction. Tempol (100 microM, a cell permeable superoxide dismutase mimetic) partially reduced the augmented Ang II response in HG exposed aortic rings, while it did not affect the Ang II responses in normal glucose (NG 5.5 mM) exposed aortic rings isolated from control rats. [3H] Ang II binding at AT1 receptors was unaltered in vascular smooth muscle membranes prepared from thoracic aorta exposed to HG for 2 h compared to NG exposed aortic rings. From our results, we conclude that high glucose concentration augments Ang II mediated contraction via AT1 receptors and reactive oxygen species partly contribute to this augmented contraction.
Arun
K H S
KH
Cardiovascular and Receptorology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Phase-X, Sector 67, S.A.S. Nagar Mohali 160 062 Punjab, India.
Kaul
C L
CL
Ramarao
P
P
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D005947:Glucose