Ramipril and Valsartan as Protective Agents against Some Complications of an Experimentally Induced Obesity in Rats

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.