AMELIORATION OF ENDOTHELIAL DYSFUNCTION ASSOCIATED WITH DIABETES MELLITUS AND HYPERTENSION BY ETORICOXIB, LORNOXICAM AND ALLOPURINOL
Abstract
Endothelial dysfunction is associated with diabetes mellitus and hypertension. Oxidative stress and augmented activity of associated enzymes like cyclooxygenase (COX) and xanthine oxidase (XO) is a major culprit. In this study, diabetes mellitus (DM) was induced by alloxan (75 mg/kg, i.v) and hypertension was induced by left renal artery (LRA) ligation in male Wistar rats. Treatment with COX inhibitors, etoricoxib (10 mg/kg, p.o), lornoxicam (4.5 mg/kg, i.p) and XO inhibitor, allopurinol (50 mg/kg, p.o) was initiated after confirming induction of diabetes and hypertension and continued for 6 weeks. Vascular reactivity to catecholamines like adrenaline (1 µg/kg), noradrenaline (1 µg/kg), and phenylephrine (1 µg/kg), was evaluated in both models wherein treated rats expressed better responses than untreated groups. In an in vitro study, relaxant response to acetylcholine (ACh) and sodium nitroprusside (SNP) was observed on isolated aortas. Relaxation to ACh was impaired in untreated groups but treated groups produced near to normal relaxant responses. In case of SNP, no significant results were obtained. Diabetes and hypertension induced significant oxidative stress reflected by increase in lipid peroxidation level and decrease in antioxidant enzymes like catalase and superoxide dismutase. Drugs treatment reversed these effects on oxidative stress indices and ameliorated endothelial dysfunction.
Keywords:
Allopurinol, diabetes, endothelial dysfunction,, etoricoxib, hypertension, lornoxicamDOI
https://doi.org/10.25004/IJPSDR.2014.060210References
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25. Katakam RG, Ujhelyi MR, Hoenig ME, Miller AW. Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am J Physiol. 1998; 275:R788-92.
26. Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond). 2005; 109:143-59.
27. Chalon S, Tejura B, Moreno H, Urae A, Blaschke TF, Hoffman BB. Role of nitric oxide in isoprenaline and sodium nitroprusside-induced relaxation in human hand veins. Br J Clin Pharmacol.1999; 47:91–8.
28. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol. 1999; 34:631-8.
29. Cardillo C, Kilcoyne CM, Cannon RO, Quyyumi AA, Panza JA. Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients. Hypertension. 1997; 30:57-63.
30. Ahmed RG. The physiological and biochemical effects of diabetes on the balance between oxidative stress and antioxidant defense system. Med J Islamic World Acad Sci. 2005; 15:31-42.
31. Hirata Y, Satonaka H. Hypertension and Oxidative Stress. Japan Med Assoc J. 2001; 44:540-5.
32. Hadi AR, Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007; 3:853-76.
33. Ozturk Hayrettin, Gezici A, Ozturk H. The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats. Hepatol Res. 2006; 34:76-83.
34. Ansari MA, Hussain SK, Mudagal MP, Goli D. Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats. Eur Rev Med Pharmacol Sci. 2013; 17:170-8.
2. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet 2005; 365:217-23.
3. Calles-Escandon J, Cipolla M. 2001. Diabetes and endothelial dysfunction: a clinical perspective. Endocr Rev. 2001; 22:36-52.
4. Puddu P, Puddu GM, Zaca F, Muscari A. Endothelial dysfunction in hypertension. Acta Cardiol. 2000; 55:221-32.
5. Cleland SJ, Connell JMC. Insulin Resistance, Hypertension and Endothelial Dysfunction. Wiley, West Sussex, 2005, pp. 465-471.
6. Szocs K. Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance. Gen Physiol Biophys. 2004; 23:265-95.
7. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010; 107:1058-70.
8. Lassegue B, Griendling KK. Reactive oxygen species in hypertension: An update. Am J Hypertens. 2004:17:852-60.
9. Tschudi MR, Mesaros M, Luscher TF, Malinski T. Direct in situ measurement of nitric oxide in mesenteric resistance arteries. Increased decomposition by superoxide in hypertension. Hypertension. 1996; 27:32-5.
10. Salvemini D, Doyle TM, Cuzzocrea S. Superoxide, peroxynitrite and oxidative/nitrative stress in inflammation. Biochem Soc Trans. 2006; 34:965-70.
11. Hink U, Oelze M, Kolb P, Bachschmid M, Zou MH, Daiber A, Mollnau H, August M, Baldus S, Tsilimingas N, Walter U, Ullrich V, Munzel T. Role of peroxynitrite in the inhibition of prostacyclin synthase in nitrate tolerance. J Am Coll Cardiol. 2003; 42:1826-34.
12. Butler R, Morris AD, Belch JJF, Hill A, Struthers AD. Allopurinol Normalizes Endothelial Dysfunction in Type 2 Diabetics With Mild Hypertension. Hypertension. 2000; 35:746-51.
13. Desco MC, Asensi M, Marquez R, Martinez-Valls J, Vento M,Pallardo FV, Sastre J, Vina J. Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. Diabetes. 2002; 51:1118-24.
14. Wallwork CJ, Parks DA, Schmid-Schonbein GW. Xanthine oxidase activity in the dexamethasone-induced hypertensive rat. Microvasc Res. 2003; 66:30-7.
15. Honda H, Ushijima D, Ishihara H, Yanase M, Kogo H. A regional variation of acetylcholine-induced relaxation in different segments of rat aorta. Physiol Behav 1997; 63:55-8.
16. Zhang LN, Vincelette J, Chen D, Gless RD, Anandan SK, Rubanyi GM, Webb HK, MacIntyre E, Wang YX. Inhibition of soluble epoxide hydrolase attenuates endothelial dysfunction in animal models of diabetes, obesity and hypertension. Eur J Pharmacol. 2011; 654:68-74.
17. Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action. J Med Food. 2003; 6:107-14.
18. Luck H. Methods of enzymatic analysis. Academic Press, New York, 1971; pp. 885– 893.
19. Kono Y. Generation of superoxide radical during autooxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 1978; 186:189-95.
20. Wills ED. Mechanism of lipid peroxide formation in animal tissues. Biochem J. 1966; 99:667– 76.
21. Gimbrone MA, Topper JN, Nagel T, Anderson KR, Garcia-Cardena G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci. 2000; 902:230-9.
22. Friedl HP, Smith DJ, Till GO, Thomson PD, Louis DS, Ward PA. Ischaemia-reperfusion in humans: appearance of xanthine oxidase activity. Am J Pathol. 1990; 136:491-5.
23. Kishi K, Inoue T. Possible mechanisms of abnormal nor-epinephrine sensitivity and reactivity of resistance vessels and the development of hypertension in spontaneously hypertensive rats: A hypothesis. Am J Hypertens. 1990; 3:202S-5S.
24. Sherman DL, Keaney JF, Biegelsen ES, Duffy SJ, Coffman JD, Vita JA. Pharmacological concentrations of ascorbic acid are required for the beneficial effects on endothelial vasomotor function in hypertension. Hypertension. 2000; 35:936–41.
25. Katakam RG, Ujhelyi MR, Hoenig ME, Miller AW. Endothelial dysfunction precedes hypertension in diet-induced insulin resistance. Am J Physiol. 1998; 275:R788-92.
26. Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond). 2005; 109:143-59.
27. Chalon S, Tejura B, Moreno H, Urae A, Blaschke TF, Hoffman BB. Role of nitric oxide in isoprenaline and sodium nitroprusside-induced relaxation in human hand veins. Br J Clin Pharmacol.1999; 47:91–8.
28. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol. 1999; 34:631-8.
29. Cardillo C, Kilcoyne CM, Cannon RO, Quyyumi AA, Panza JA. Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients. Hypertension. 1997; 30:57-63.
30. Ahmed RG. The physiological and biochemical effects of diabetes on the balance between oxidative stress and antioxidant defense system. Med J Islamic World Acad Sci. 2005; 15:31-42.
31. Hirata Y, Satonaka H. Hypertension and Oxidative Stress. Japan Med Assoc J. 2001; 44:540-5.
32. Hadi AR, Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag. 2007; 3:853-76.
33. Ozturk Hayrettin, Gezici A, Ozturk H. The effect of celecoxib, a selective COX-2 inhibitor, on liver ischemia/reperfusion-induced oxidative stress in rats. Hepatol Res. 2006; 34:76-83.
34. Ansari MA, Hussain SK, Mudagal MP, Goli D. Neuroprotective effect of allopurinol and nimesulide against cerebral ischemic reperfusion injury in diabetic rats. Eur Rev Med Pharmacol Sci. 2013; 17:170-8.
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01-04-2014
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“AMELIORATION OF ENDOTHELIAL DYSFUNCTION ASSOCIATED WITH DIABETES MELLITUS AND HYPERTENSION BY ETORICOXIB, LORNOXICAM AND ALLOPURINOL”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 6, no. 2, Apr. 2014, pp. 132-6, https://doi.org/10.25004/IJPSDR.2014.060210.
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How to Cite
“AMELIORATION OF ENDOTHELIAL DYSFUNCTION ASSOCIATED WITH DIABETES MELLITUS AND HYPERTENSION BY ETORICOXIB, LORNOXICAM AND ALLOPURINOL”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 6, no. 2, Apr. 2014, pp. 132-6, https://doi.org/10.25004/IJPSDR.2014.060210.
