Abstract
The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor γ agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.
Similar content being viewed by others
References
Albertini, J. P., McMorn, S. O., Chen, H., Mather, R. A., and Valensi, P., Effect of rosiglitazone on factors related to endothelial dysfunction in patients with type 2 diabetes mellitus. Atherosclerosis, 195, E159–166 (2007).
Balakumar, P., Kaur, T., and Singh, M., Potential targets to modulate vascular endothelial dysfunction: current perspectives and future directions. Toxicology, 245, 49–64 (2008).
Barchowsky, A., Klei, L. R., Dudek, E. J., Swartz, H. M., and James, P. E., Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic. Biol. Med., 27, 1405–1412 (1999).
Chen, C. J., Hsueh, Y. M., Lai, M. S., Shyu, M. P., Chen, S. Y., Wu, M. M., Kuo, T. L., and Tai, T. Y., Increased prevalence of hypertension and long-term arsenic exposure. Hypertension, 25, 53–60 (1995).
Chen, Y., Parvez, F., Gamble, M., Islam, T., Ahmed, A., Argos, M., Graziano, J. H., and Ahsan, H., Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Toxicol. Appl. Pharmacol., 239, 184–192 (2009).
Clayden, E. C., Practical section cutting and staining. Churchill Livingstone, London, pp. 115, (1971).
Davignon, J. and Ganz, P., Role of endothelial dysfunction in atherosclerosis. Circulation, 109, 11127–11132 (2004).
Desjardins, F. and Balligand, J. L., Nitric oxide-dependent endothelial function and cardiovascular disease. Acta Clin. Belg., 61, 326–334 (2006).
Duvall, W. L., Endothelial dysfunction and antioxidants. Mt. Sinai J. Med., 72, 71–80 (2005).
Gingerich, S. and Krukoff, T. L., Estrogen modulates endothelial and neuronal nitric oxide synthase expression via an estrogen receptor beta-dependent mechanism in hypothalamic slice cultures. Endocrinology, 146, 2933–2941 (2005).
Gonon, A. T., Bulhak, A., Labruto, F., Sjöquist, P. O., and Pernow J., Cardioprotection mediated by rosiglitazone, a peroxisome proliferator-activated receptor gamma ligand, in relation to nitric oxide. Basic Res. Cardiol., 102, 80–89 (2007).
Grossini, E., Molinari, C., Caimmi P. P., Uberti, F., and Vacca, G., Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial KATP channel. Br. J. Pharmacol., 156, 250–261 (2009).
Hansen, E. S., International commission for protection against environmental mutagens and carcinogens ICPEMC working paper 7/1/2. Shared risk factors for cancer and atherosclerosis-a review of the epidemiological evidence. Mutat. Res., 239, 163–179 (1990).
Hwang, J., Kleinhenz, D. J., Rupnow, H. L., Campbell, A. G., Thulé, P. M., Sutliff, R. L., and Hart, C. M., The PPAR gamma ligand, rosiglitazone, reduces vascular oxidative stress and NADPH oxidase expression in diabetic mice. Vascul. Pharmacol., 46, 456–462 (2007).
Izquierdo-Vega, J. A., Soto, C. A., Sanchez-Peña, L. C., and Del Razo, L. M., Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite. Toxicol. Lett., 160, 135–142 (2006).
Jermendy, G., PPARγ agonists-Antidiabetic drugs with a potential role in the treatment of diseases other than diabetes. Diabetes. Res. Clin. Pract., 78, S29–39 (2007).
Jindal, S., Singh, M., and Balakumar, P., Effect of bis (maltolato) oxovanadium (BMOV) in uric acid and sodium arsenite-induced vascular endothelial dysfunction in rats. Int. J. Cardiol., 128, 283–291 (2008).
Jollow, D., Mitchell, L., Zampaglione, N., and Gillete, J., Bromobenze induced liver necrosis: protective role of glutathione and evidence for 3,4-bromobenzenoxide as the hepatotoxic intermediate. Pharmacol., 11, 151–169 (1974).
Kashyap, V. S., Reil, T. D., Moore, W. S., Hoang, T. X., Gelabert, H. A., Byrns. R. E., Ignarro. L. J., and Freischlag. J. A., Acute arterial thrombosis causes endothelial dysfunction: a new paradigm for thrombolytic therapy. J. Vasc. Surg., 34, 323–329 (2001).
Kawashima, S. and Yokoyama, M., Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 24, 998–1005 (2004).
Kinoshita, H., Azma, T., Iranami, H., Nakahata, K., Kimoto, Y., Dojo, M., Yuge, O., and Hatano, Y., Synthetic peroxisome proliferator-activated receptor-gamma agonists restore impaired vasorelaxation via ATP-sensitive K+ channels by high glucose. J. Pharmacol. Exp. Ther., 318, 312–318 (2006).
Lee, P. C., Ho, I. C., and Lee, T. C., Oxidative stress mediates sodium arsenite-induced expression of heme oxygenase-1, monocyte chemoattractant protein-1, and interleukin-6 in vascular smooth muscle cells. Toxicol. Sci., 85, 541–550 (2005).
Ma, F. X., Liu, L. Y., and Xiong, X. M., Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein. Acta Pharmacol. Sin., 24, 1027–1032 (2003).
Maytin, M., Leopold, J., and Loscalzo, J., Oxidant stress in the vasculature. Curr. Atheroscler. Rep., 1, 156–164 (1999).
Mittra, S. and Singh, M., Possible mechanism of captopril induced endothelium-dependent relaxation in isolated rabbit aorta. Mol. Cell. Biochem., 183, 63–67 (1998).
Panunti, B. and Fonseca, V., Effects of PPAR gamma agonists on cardiovascular function in obese, non-diabetic patients. Vascul. Pharmacol., 45, 29–35 (2006).
Papaharalambus, C. A. and Griendling, K. K., Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc. Med., 17, 48–54 (2007).
Pesic, S., Radenkovic, M., and Grbovic, L., Endothelial dysfunction: mechanisms of development and therapeutic options. Med. Pregl., 59, 335–341 (2006).
Pieper, G. M., Acute amelioration of diabetic endothelial dysfunction with a derivative of the nitric oxide synthase cofactor, tetrahydrobiopterin. J. Cardiovasc. Pharmacol., 29, 8–15 (1997).
Potenza, M. A., Gagliardi, S., De Benedictis, L., Zigrino, A., Tiravanti, E., Colantuono, G., Federici, A., Lorusso, L., Benagiano, V., Quon, M. J., and Montagnani, M., Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature. Am. J. Physiol. Endocrinol. Metab., 297, E685–694 (2009).
Puddu, P., Puddu, G.M., and Muscari, A., Peroxisome proliferator-activated receptors: are they involved in atherosclerosis progression? Int. J. Cardiol., 90, 133–140 (2003).
Ríos-Vázquez, R., Marzoa-Rivas, R., Gil-Ortega, I., and Kaski, J. C., Peroxisome proliferator-activated receptor-gamma agonists for management and prevention of vascular disease in patients with and without diabetes mellitus. Am. J. Cardiovasc. Drugs, 6, 231–242 (2006).
Rush, J. W., Denniss, S. G., and Graham, D. A., Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and to physical activity. Can. J. Appl. Physiol., 30, 442–474 (2005).
Sastry, K. V., Moudgal, R. P., Mohan, J., Tyagi, J. S., and Rao, G. S., Spectrophotometric of serum nitrite and nitrate by copper-cadmium alloy. Anal. Biochem., 306, 79–82 (2002).
Satoh, H., Tsukamoto, K., Hashimoto, Y., Hashimoto, N., Togo, M., Hara, M., Maekawa, H., Isoo, N., Kimura, S., and Watanabe, T., Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: a new possible role of PPAR gamma on vascular endothelial function. Biochem. Biophys. Res. Commun., 254, 757–763 (1999).
Savoia, C. and Schiffrin, E. L., Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions. Clin. Sci. (Lond)., 112, 375–384 (2007).
Shah, D. I. and Singh, M., Possible role of Akt to improve vascular endothelial dysfunction in diabetic and hyperhomocysteinemic rats. Mol. Cell. Biochem., 295, 65–74 (2007).
Smith, K. R., Klei, L. R., and Barchowsky, A., Arsenite stimulates plasma membrane NADPH oxidase in vascular endothelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol., 280, L442–449 (2001).
Touyz, R. M. and Schiffrin, E. L., Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications. Vascul. Pharmacol., 45, 19–28 (2006).
Tsou, T. C., Tsai, F. Y., Hsieh, Y. W., Li, L. A., Yeh, S. C., and Chang, L. W., Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase. Toxicol. Appl. Pharmacol., 208, 277–284 (2005).
Vanhoutte, P. M., Aging and endothelial dysfunction. Euro. Heart J., 4, A8–17 (2004).
Verma, S. and Szmitko, P. E., The vascular biology of peroxisome proliferators activated receptors: Modulation of atherosclerosis. Can. J. Cardiol., 22, B12–17 (2006).
Wang, H. D., Pagano, P. J., Du, Y., Cayatte, A. J., Quinn, M. T., Brecher, P., and Cohen, R. A., Superoxide anion from the adventitia of the rat thoracic aorta inactivates nitric oxide. Circ. Res., 82, 810–818 (1998).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kaur, T., Goel, R.K. & Balakumar, P. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction. Arch. Pharm. Res. 33, 611–618 (2010). https://doi.org/10.1007/s12272-010-0416-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-010-0416-x