Objectives: Our work aimed to study the effect of experimentally induced obesity on the rate of advanced glycated end products (AGEs) formation and the activity of angiotensin converting enzyme (ACE) and its relation to oxidative stress and also to evaluate the protective effect of ramipril (an angiotensin converting enzyme inhibitor), valsartan [an angiotensin II blocker; AT1 receptor blocker), and their combination on these obese animals. Materials and Methods: The present study was conducted on ten female albino rats fed on standard chow as a control group and fifty obese animals received for sixteen weeks high fat diet alone or in concomitant combination with either ramipril (2 mg/kg/day or 0.25 mg/kg) or valsartan (0.30 mg/kg/day) or the combination of both drugs (0.25 mg/kg of ramipril and 0.30 mg/kg of valsartan daily for sixteen weeks). Blood, kidney and aortic AGEs, ACE activity and advanced oxidation protein products (AOPPs) were measured. Results: The obtained results showed increase in triacylglycerols (TGs) levels (p<0.043) in the obese animals versus the control group. The total blood cholesterol (TC) and LDL-cholesterol (LDL-C) levels, also, were significantly higher (p<0.0001) in obese animals compared to the corresponding values in controls, with a significant reduction in their levels in all treated groups except in group IV (p=.041) when compared to the control group. On the other hand, HDL-cholesterol (HDL-C) was significantly lower (p<0.0001) in the obese animals compared to its level in the controls. The obese animals showed significant increase in their blood glucose and serum insulin levels when compared to the controls [(p<0.037) and (p<0.045), respectively]. The results, also, revealed that obesity was associated with a statistically significant increase in the blood, kidney and aortic tissue levels of AGEs, ACE and AOPPs compared to their corresponding values in the control group. Treatment with ramipril, valsartan and their combination caused significant reduction in serum and tissue levels of both AGEs and AOPPs when compared with the obese group. On the other hand, ACE activity was markedly reduced following the administration of ramipril alone or when it is combined with valsartan, while the administration of valsartan alone showed no significant effect on the activity of ACE when compared to the obese group. Moreover, combination of ramipril (at a submaximal antihypertensive dose of 0.25 mg/kg/day) with valsartan produce a marked reduction in all parameters examined compared to valsartan alone. Conclusion: combination of ramipril and valsartan showed more therapeutic effect compared to individual therapy with ACE inhibitor or AT1 receptor blocker.
Published in | American Journal of Life Sciences (Volume 2, Issue 4) |
DOI | 10.11648/j.ajls.20140204.18 |
Page(s) | 241-250 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2014. Published by Science Publishing Group |
Ramipril, Valsartan, Obesity, AGE, ACE, AOPPs
[1] | Aronne LJ. Epidemiology, morbidity and treatment of overweight and obesity. J. Clin. Psychiatry. 2001; 62:13-22 |
[2] | Zanella MT, Kohlmann O and Ribewiro AB. treatment of obesity hypertension and diabetes syndrome. Hypertension. 2002; 38:705 |
[3] | Lopez de Fez, CM, Gaztelu MT, Rubio T, Castano A, and Navar. Mechanisms of hypertension in obesity. An. Sist. Sanit. 2004; 27:211-219 |
[4] | Mazzolai L, Nussberger J, Aubert JF, Brunner DB, Gabbiani G, Brunner HR, and Pedrazzini T. Blood pressure-independent cardiac hypertrophy induced by locally activated rennin -angiotensin system. Hypertension. 1998; 31:1324 |
[5] | Engeli S, Negrel R and Sharm G. Physiology and pathophysiology of the adipose tissue Rennin-Angiotensin System. Hypertension. 2000; 35: 1270-1275 |
[6] | Hooper NM and Turner AJ. An ACE structure. Nat. Struct. Biol. 2003; 10: 155-157 |
[7] | Riordan JF. Angiotensin-1-converting enzyme and its relatives. Genome Biol. 2003; 4: 225-231 |
[8] | Wysocki YMJ, Naaz P, Salabat MR, Michael S, Pointe L and Battle D. Increased ACE 2 and decreaed ACE protein in renal tubules from diabetic mice: a reno- protective combination?. Hypertension. 2004; 43: 1120-1126 |
[9] | Anderson NH, Poulsen PL, Knudsen ST, Poulsen SH, Hansen, Helleberg, KW and Mogensen CE. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes. Diabetes Care. 2005; 28: 273-277 |
[10] | Laverman GD, Remuzzi G and Ruggenenti P. ACE inhibition versus angiotensin receptor blockade: which is better for renal and cardiovascular protection?. J. Am. Soc. Nephrol. 2004; 15: S64 |
[11] | Fuller JH, Shipley MJ, Rose G, Jarrett RJ and Keen H. Coronary heart disease risk and impaired glucose tolerance the Whitehall study. Lancet. 1980; 1: 1373 |
[12] | Mitsuhashi T, Nakayama H, Itoh T, Kuwajima S, Aoki S, Atsumi T and Koike T. Immunochemical detection of advanced glycation end products of renal cortex from streptozotocin-induced diabetic rats. Diabetes 1993; 42:826-832 |
[13] | Turk Z, Sesto M, Skodiar J, Ferencak G, Pokupec R, Turk N and Rukavina S. Products of advanced glycation in patients with type 2 diabetes and vascular disease. Assoc. Clin. Biochem., 2003; 40: 552-559 |
[14] | Huang JS, Guh JY, Chen HC, Hung WC, Lai YH and Chuang LY. Role of receptor for advanced glycation end product (RAGE) and the JAK/STAT signaling pathway in AGE-induced collagen production in NRK-49F cells. J. Cell Biochem. 2001; 81:102 |
[15] | Schmidt AM, Yan SD, Wautier JL and Stern D. Activation of receptor for advanced glycation end products: a mechanism for vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circulation Research 1999; 84: 489-497 |
[16] | Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM and Wautier JL. Activation of NADPH oxidase by ACE links oxidant stress to altered gene expression via RAGE. AM. J. Physiol. Endocrinol. Metab. 2001; 280: E685-E694 |
[17] | Stocker R, John F and Keaney JR. Role of oxidative modifications in atherosclerosis. Physiol. Rev. 2004; 84:1381-1478 |
[18] | Kalousova M, Zima T, Tesar V and Lachmanova J. Advanced glycation end products and advanced oxidation protein products in hemodialyzed patients. Blood Purif. 2001; 20: 531-536 |
[19] | Fialova L, Kalousova M, Soukupova J, Malbohan I, Krofta L, Mikulikova L, Horejsova H, Stipek S and Zima T. Levels of advanced oxidation protein products (AOPP) in the forst trimester of pregnancy. Sb Lek. 2003; 104(1): 95-102 |
[20] | Ylma IA, Akcay T, Akatay U, Telci A, Ataus S and Yalcin V. Relation between bladder cancer and protein oxidation. International Urology and Nephrology 2003; 35: 345-350 |
[21] | Davies M, Brown B, Cauka R, Howkin C, Headless h, Woods A, Martin R and Philip M. Mechanism of protein oxidation. EPR Group 2003; 4:1-2 |
[22] | Forbes JM, Cooper ME, Thallas V, Burns WC, Thomas MC, Brammar GC, Lee F, Grant SL, Burrell LA, Jerums G and Osicka TM. Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetes. Diabetes 2002; 51:3274-3282 |
[23] | Leiter LA and Lewanczuk RZ. Of the rennin angiotensin system and reactive oxygen species type II diabetes and angiotensin II inhibition. AM. J. Hypertension 2005; 18: 121-128 |
[24] | Wang CH, Leung N, Lapointe N, Szeto L, Uffelman KD, Giacca A, Rouleau JL and Lewis GF. Vasopeptidase inhibitor omapatrilat induces profound insulin sensitization and increases myocardial glucose uptake in Zucker fatty rats: Studies comparing a vasopeptidase inhibitor, ACE inhibitor and angiotensin II type I receptor blocker. Circulation 2003; 107: 1923 |
[25] | Mervaala EM, Teravainen TL, Malmberg L, Laakso J, Vapaatalo H and Karppanen H. Cardiovascular effects of a low dose combination of ramipril and felodipine in spontaneously hypertensive rats. BR. J. Pharmacol.,m 1997; 121: 503-510 |
[26] | Forbes JM, Thomas MC, Thrope SR, Alderson NL and Cooper ME. The effects of valsartan on the accumulation OF circulating and renal advanced glycation end products in experimental diabetes. Kidney Int. (Suppl.) 2004; 92:S105 |
[27] | Lemmonnier D. Effect of age, sex and site on the cellularity of adipose tissue in mice and rats rendered obese by high fat diet. J. Clin. Invest. 1972; 51: 2907 |
[28] | Ikemoto S, Talahasi M, TsunodaN, Maruyama K, Itakura H and Ezaky O. High fat diet induced hyperglycemia and obesity in mice: differential effects of dietary oils. Metabolism 1996; 45: 1539 |
[29] | Bradford MM. A rapid and sensitive method for the quantitation of microorganisms' quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976; 72:248 |
[30] | Varley H, Gowenlock H and Bell M. Determination of plasma glucose by oxidase method. In practical Clinical Biochemistry Vol. 2, 5th edition, William Medical Books Ltd, London. 1980; 385-396 |
[31] | Engvall E, Jonsson K, and Perlman P. Enzyme- linked immunosorbent assay. II. Quantitative assay of protein antigen, immunoglobulin G, by means of enzyme-labeled antigen and antibody-coated tubes. Biochim. Biophys. Acta 1971; 251:427-434 |
[32] | Nakayama H, Mitsuhashi T, Kuwajima S, Aoki S, Kuroda Y, Itoh T and Nakagawa S. Immunochemical detection of advanced glycation end products in lens crystalline from streptozotocin-induced diabetic rat. Diabetes 1993; 42: 345-350 |
[33] | Edwards CA and O’Brein JR. Modified assay for determination of hydroxyproline in tissue hydrolysate. Clin. Chim. Acta 1980; 104: 161-167 |
[34] | Witko-Sarat V, Friedlander M, Capeillere-Blandin C, Nguyen-Khoa T, Nguyen AT, Zingraff J, Jungers P and Descamps-Latscha B. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996; 49: 1304-1313 |
[35] | Oleveira EM, Santos RAS and Krieger JE. Standardization of a fluorimetric assay for determination of tissue angiotensin converting enzyme activity in rats. Braz. J. Med. Biol. Res. 2000; 33:755 |
[36] | Gaundleger ML and Wthenen S. Decreased insulin binding, glucose transport and glucose metabolism in soleus muscle of rats fed a high fat diet. Diabetes 1992; 31: 232-237 |
[37] | Salans LB, Foley LT, Wardzala LJ and Cushman SW. Effects of dietary composition on glucose metabolism in rat adipose cells. Am. J. Physiol. 1981; 240: E175-E183 |
[38] | Valensi P, Derobert E, Genthon R and Riou JP. Effect of raipril on insulin sensitivity in obese patients. Time course study of glucose infusion rate during euglycemic hyperinsulinemic clamp. Diabetes Metab. 1996; 22: 197-200 |
[39] | Brown NJ, Kumar S, Painter CA and Vaughan DE. ACE inhibition versus angiotensin type I receptor antagonism. Hypertension 2002; 40: 1-2 |
[40] | Boivin A and Deshaies Y. Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are associated. Metabolism 1995; 44(12): 1540-1547 |
[41] | Schnack C, Hoffmann W, Hopmeier P and Schernthaner G. Renal and metabolic effects of 1-year treatment with ramipril and atenolol in NIDDM patients with microalbuminuria. Diabetologia 1996; 39:1611-1616 |
[42] | Veliga-Asimi Z and Heljic B. The effects of valsartan on lipid profile in normotensive type 2 diabetic patients. Med. Arh. 2005; 9:311 |
[43] | Engeli S, Negrel R and Sharm, G. Physiology and Pathophysiology of the adipose tissues Rennin-Angiotensin System. Hypertension 2000; 35:1270-1275 |
[44] | Tan K, CB, Chow WS, Tam S, Bucala R and Betterridge J. Association between acute phase reactants and advanced glycation end products in type 2 diabetes. Diabetes Care 2004; 27: 223-228 |
[45] | Wolff SP. Diabetes mellitus and free radicals: Free radicals, transition metals and oxidative stress in the etiology of diabetes mellitus and complications. Br. Med. Bull. 1993; 49:642-652 |
[46] | Hayek T, Pavlotzky E, Hamoud S, Coleman R, Keidar S, aviram M and Kaplan M. Tissue ACE deficiency leads to a reduction in oxidative stress and in atherosclerosis: Studies in ACE-Knockout mice type 2 diabetes. Atherosclerosis, thrombosis and Vascular Biology 2003; 23: 2090-2096 |
[47] | Onozato ML, Tojo A, Goto A, Fujita T and Wilcox CS. Oxidative stress and nitric oxide synthase in rat diabetic nephropathy: Effects of ACE1 and ARB. Kidney Int. 2002; 61: 186 |
[48] | Zou MH, Shi C and Cohen RA. High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H2 receptor mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Diabetes 2002; 51:198-203 |
[49] | Sebekova K, Gazdikova K, Syrova D, Blazicek P, Schinzel R, Heidland A, Spustova A and Dzurik R. Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidative stress and potential modulation of advanced glycation end products. J. Human hypertension 2003; 17: 265-270 |
[50] | Miyata T, Strihou CY, Ueda Y, Ichimori K, Inagi R, Onogi H, Ishikawa N, Nangaku M and Kurokawa K. Angiotensin II receptor antagonists and ACE inhibitors lower invitro the formation of advanced glycation end products; Biochemical mechanisms. J. Am. Soc. Nephrol., 2002; 13:2478-2487 |
[51] | Nakayama M, Inogushi T, Obayashi K, Sumimoto H and Nawata H. increased expression of NAD(P)H oxidase in islets of animal models of type 2 diabetes and its improvement by an AT1 receptor antagonist. Biochem.biophys. Res. Common. 2005; 332(4): 927-933 |
[52] | Imanishi T, Hano T and Nishio H. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress. J. Hypertension 2005; 231: 97-104 |
[53] | Blendea MC, Jacobs D, Stump CS, McFarlane SI, Ogrin C, Bahtyiar G, Stas S, Kumar P, Sha Q, Ferrario CM and Sowers JR. Abrogation of oxidative stress improves insulin sensitivity in the Ren-2 rat model of tissue angiotensin II over-expression. Am. J. Physiol. Endocrinol. Metab. 2005; 288: E353 |
[54] | Davie AP, Dargie HJ and McMurray JJ. Role of bradykinin in the vasodilator effects of losartan and enalapril in patients with heart failure. Circulation 1999; 00:268-273 |
[55] | Yagi S, Morita T and Katayama S. Combined treatment with an AT1 receptor and ACE1 has an additive effect on inhibiting suppression of oxidative stress. Hypertens. Res. 2004; 27:129 |
[56] | McInnes GT. Clinical potential: of ACEI or angiotensin II antagonist? J. Hypertens. 2001; (suppl.) 19(1): 561- 567 |
APA Style
Said Al-Dalaen, Aiman Al-Qtaitat, Samir Mahgoub, Nedal Alnawaiseh, Jehad Al-Shuneigat, et al. (2014). Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats. American Journal of Life Sciences, 2(4), 241-250. https://doi.org/10.11648/j.ajls.20140204.18
ACS Style
Said Al-Dalaen; Aiman Al-Qtaitat; Samir Mahgoub; Nedal Alnawaiseh; Jehad Al-Shuneigat, et al. Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats. Am. J. Life Sci. 2014, 2(4), 241-250. doi: 10.11648/j.ajls.20140204.18
AMA Style
Said Al-Dalaen, Aiman Al-Qtaitat, Samir Mahgoub, Nedal Alnawaiseh, Jehad Al-Shuneigat, et al. Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats. Am J Life Sci. 2014;2(4):241-250. doi: 10.11648/j.ajls.20140204.18
@article{10.11648/j.ajls.20140204.18, author = {Said Al-Dalaen and Aiman Al-Qtaitat and Samir Mahgoub and Nedal Alnawaiseh and Jehad Al-Shuneigat and Samih Sarayreh and Yousef Sarayreh}, title = {Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats}, journal = {American Journal of Life Sciences}, volume = {2}, number = {4}, pages = {241-250}, doi = {10.11648/j.ajls.20140204.18}, url = {https://doi.org/10.11648/j.ajls.20140204.18}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.20140204.18}, abstract = {Objectives: Our work aimed to study the effect of experimentally induced obesity on the rate of advanced glycated end products (AGEs) formation and the activity of angiotensin converting enzyme (ACE) and its relation to oxidative stress and also to evaluate the protective effect of ramipril (an angiotensin converting enzyme inhibitor), valsartan [an angiotensin II blocker; AT1 receptor blocker), and their combination on these obese animals. Materials and Methods: The present study was conducted on ten female albino rats fed on standard chow as a control group and fifty obese animals received for sixteen weeks high fat diet alone or in concomitant combination with either ramipril (2 mg/kg/day or 0.25 mg/kg) or valsartan (0.30 mg/kg/day) or the combination of both drugs (0.25 mg/kg of ramipril and 0.30 mg/kg of valsartan daily for sixteen weeks). Blood, kidney and aortic AGEs, ACE activity and advanced oxidation protein products (AOPPs) were measured. Results: The obtained results showed increase in triacylglycerols (TGs) levels (p<0.043) in the obese animals versus the control group. The total blood cholesterol (TC) and LDL-cholesterol (LDL-C) levels, also, were significantly higher (p<0.0001) in obese animals compared to the corresponding values in controls, with a significant reduction in their levels in all treated groups except in group IV (p=.041) when compared to the control group. On the other hand, HDL-cholesterol (HDL-C) was significantly lower (p<0.0001) in the obese animals compared to its level in the controls. The obese animals showed significant increase in their blood glucose and serum insulin levels when compared to the controls [(p<0.037) and (p<0.045), respectively]. The results, also, revealed that obesity was associated with a statistically significant increase in the blood, kidney and aortic tissue levels of AGEs, ACE and AOPPs compared to their corresponding values in the control group. Treatment with ramipril, valsartan and their combination caused significant reduction in serum and tissue levels of both AGEs and AOPPs when compared with the obese group. On the other hand, ACE activity was markedly reduced following the administration of ramipril alone or when it is combined with valsartan, while the administration of valsartan alone showed no significant effect on the activity of ACE when compared to the obese group. Moreover, combination of ramipril (at a submaximal antihypertensive dose of 0.25 mg/kg/day) with valsartan produce a marked reduction in all parameters examined compared to valsartan alone. Conclusion: combination of ramipril and valsartan showed more therapeutic effect compared to individual therapy with ACE inhibitor or AT1 receptor blocker.}, year = {2014} }
TY - JOUR T1 - Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats AU - Said Al-Dalaen AU - Aiman Al-Qtaitat AU - Samir Mahgoub AU - Nedal Alnawaiseh AU - Jehad Al-Shuneigat AU - Samih Sarayreh AU - Yousef Sarayreh Y1 - 2014/09/10 PY - 2014 N1 - https://doi.org/10.11648/j.ajls.20140204.18 DO - 10.11648/j.ajls.20140204.18 T2 - American Journal of Life Sciences JF - American Journal of Life Sciences JO - American Journal of Life Sciences SP - 241 EP - 250 PB - Science Publishing Group SN - 2328-5737 UR - https://doi.org/10.11648/j.ajls.20140204.18 AB - Objectives: Our work aimed to study the effect of experimentally induced obesity on the rate of advanced glycated end products (AGEs) formation and the activity of angiotensin converting enzyme (ACE) and its relation to oxidative stress and also to evaluate the protective effect of ramipril (an angiotensin converting enzyme inhibitor), valsartan [an angiotensin II blocker; AT1 receptor blocker), and their combination on these obese animals. Materials and Methods: The present study was conducted on ten female albino rats fed on standard chow as a control group and fifty obese animals received for sixteen weeks high fat diet alone or in concomitant combination with either ramipril (2 mg/kg/day or 0.25 mg/kg) or valsartan (0.30 mg/kg/day) or the combination of both drugs (0.25 mg/kg of ramipril and 0.30 mg/kg of valsartan daily for sixteen weeks). Blood, kidney and aortic AGEs, ACE activity and advanced oxidation protein products (AOPPs) were measured. Results: The obtained results showed increase in triacylglycerols (TGs) levels (p<0.043) in the obese animals versus the control group. The total blood cholesterol (TC) and LDL-cholesterol (LDL-C) levels, also, were significantly higher (p<0.0001) in obese animals compared to the corresponding values in controls, with a significant reduction in their levels in all treated groups except in group IV (p=.041) when compared to the control group. On the other hand, HDL-cholesterol (HDL-C) was significantly lower (p<0.0001) in the obese animals compared to its level in the controls. The obese animals showed significant increase in their blood glucose and serum insulin levels when compared to the controls [(p<0.037) and (p<0.045), respectively]. The results, also, revealed that obesity was associated with a statistically significant increase in the blood, kidney and aortic tissue levels of AGEs, ACE and AOPPs compared to their corresponding values in the control group. Treatment with ramipril, valsartan and their combination caused significant reduction in serum and tissue levels of both AGEs and AOPPs when compared with the obese group. On the other hand, ACE activity was markedly reduced following the administration of ramipril alone or when it is combined with valsartan, while the administration of valsartan alone showed no significant effect on the activity of ACE when compared to the obese group. Moreover, combination of ramipril (at a submaximal antihypertensive dose of 0.25 mg/kg/day) with valsartan produce a marked reduction in all parameters examined compared to valsartan alone. Conclusion: combination of ramipril and valsartan showed more therapeutic effect compared to individual therapy with ACE inhibitor or AT1 receptor blocker. VL - 2 IS - 4 ER -