Journal of Pharmacology and Toxicology1816-496x2152-100xAcademic Journals Inc.10.3923/jpt.2007.437.446BalakumarPitchai JindalSeema SinghManjeet 5200725The present study has been designed to investigate the potential of in-vivo administration of uric acid and sodium arsenite in the development of vascular endothelial dysfunction (VED) in rats. The uric acid (100, 150, 200 mg kg-1 day-1, i.p., 3 weeks) and sodium arsenite (1, 1.5, 2 mg kg-1 day-1, i.p., 2 weeks) were administered to rats. Vascular endothelial dysfunction was assessed by employing isolated aortic ring preparation, electron microscopy of thoracic aorta and estimating serum concentration of nitrite/nitrate. Further, serum thiobarbituric acid reactive substances (TBARS) and aortic production of superoxide anion were estimated to assess oxidative stress. High dose of uric acid (200 mg kg-1 day-1, i.p., 3 weeks) and sodium arsenite (2 mg kg-1 day-1, i.p., 2 weeks) were noted to produce high mortality rate (>85%) in animals. On the other hand, less mortality rate (<5%) was observed in animals treated with uric acid (100, 150 mg kg-1 day-1, i.p., 3 weeks) and sodium arsenite (1, 1.5 mg kg-1 day-1, i.p., 2 weeks). Moreover, uric acid (100, 150 mg kg-1 day-1, i.p., 3 weeks) and sodium arsenite (1, 1.5 mg kg-1 day-1, i.p., 2 weeks) were noted to produce vascular endothelial dysfunction by attenuating acetylcholine-induced endothelium dependent relaxation, impairing the integrity of vascular endothelial lining, decreasing serum nitrite/nitrate concentration and increasing serum TBARS and aortic superoxide anion generation. Hence, it may be concluded that uric acid (100 to 150 mg kg-1 day-1, i.p., 3 weeks) and sodium arsenite (1 to 1.5 mg kg-1 day-1, i.p., 2 weeks) may be employed as potential chemically-induced models to produce vascular endothelial dysfunction in rats.]]>Abernathy, C.O., Y.P. Liu, D. Longfellow, H.V. Aposhian and B. Beck et al.,1999107593597Balakumar, P., S. Jindal, D.I. Shah and M. Singh,200721220Bombeli, T., M. Mueller and A. Haeberli,199777408423Bonetti, P.O., L.O. Lerman and A. Lerman,200323168175Bugiardini, R., O. Manfrini, C. Pizzi, F. Fontana and G. Morgagni,200410925182523Cai, H. and D.G. Harrison,200087840844Caramori, P.R.A. and A.J. Zago,200075173182Corry, D.B. and M.L. Tuck,20068116119Cosentino, F., S. Rubatta, C. Savoia, V. Venturelli, E. Pagannonne and M. Volpe,200138S75S78Danon, D. and E. Skutelsky,19762754763David, G.F., J. Herbert and G.D. Wright,19731157997De Vriese, A.S., T.J. Verbeuren, J.V. de Voorde, N.H. Lameire and P.M. Vanhoutte,2000130963974Endemann, D.H. and E.L. Schiffrin,20041519831992Faraci, F.M. and S.R. Lentz,200435345347Feletou, M. and P.M. Vanhoutte,2006291H985H1002Furchgott, R.F. and J.V. Zawadzki,1980288373376Guerci, B., P. Bohme, S.A. Kearney, F. Zannad and P. Drouin,200127436447Hamilton, C.A., M.J. Brosnan, M. McIntyre, D. Graham and A.F. Dominiczak,200137529534Harrison, D.G.,199720I11117Ignarro, L.J., R.E. Byrns, G.M. Buga, K.S. Wood and G. Chaudhuri,1988244181189Kanellis, J. and D.H. Kang,2005253942Khosla, U.M., S. Zharikov, J.L. Finch, T. Nakagawa and C. Roncal et al.,20056717391742Lerman, A. and A.M. Zeiher,2005111363368Lin, K.C., H.M. Tsao, C.H. Chen and P. Chou,20043111521158Luscher, T.F. and M. Barton,199720310Lynn, S., J.R. Gurr, H.T. Lai and K.Y Jan,200086514519Ma, F.X., L.Y. Liu and X.M. Xiong,20032410271032Madamanchi, N.R., A. Vendrov and M.S. Runge,2005252938Masaki, T.,199535235255Mittra, S. and M. Singh,19981836367Nakagami, H., Y. Kaneda, T. Ogihara and R. Morishita,200515963Pieper, G.M.,199729815Sainani, G.S. and V.G. Maru,200452966969Sanchez-Lozada, L.G., T. Nakagawa, D.H. Kang, D.I. Feig and M.O. Franco et al.,2006153033Sastry, K.V.H., R.P. Moudgal, J. Mohan, J.S. Tyagi and G.S. Rao,20023067982Schiller, N.K., A.M. Timothy, I.L. Chen, J.C. Rice and D.L. Akers et al.,1999277H740H748Shah, D.I. and M. Singh,2006373221226Spieker, L.E., T.F. Luscher and G. Noll,200138S35S41Tsou, T.C., F.Y. Tsai, Y.W. Hsieh, L.A. Li, S.C. Yeh and L.W. Chang,2005208277288Vane, J.R., E.E. Anggard and R.M. Botting,19903232736Wang, H.D., P.J. Pagano, Y. Du, A.J. Cayatte, M.T Quinn, P. Brecher and R.A. Cohen,199882810818Yang, Z. and X.F. Ming,200645356