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Abstract
Hypertension is a major risk factor of high prevalence worldwide for cardiovascular disease. Impaired endothelial function is intimately associated with the development of hypertension and atherosclerosis. Angiotensin - converting enzyme inhibitors are extensively used to improve clinical outcome of patients with several cardiovascular diseases. We attempt a comparative study of drug-drug interaction between two different subtypes of angiotensin enzyme inhibitors, lisinopril and ramipril when combined with aspirin carried out on L - nitro arginine methyl ester (L - NAME) - induced hypertension in rats. The effect of this drug combination was tested on the reversal of endothelial dysfunction and on coagulation profile. The drugs were given P. O. for 4- weeks, lisinopril and ramipril were given in a dose of 20 mg/kg/day, while aspirin was given in a dose of 5 mg/kg/day. The selected drugs were given simultaneously with L - NAME 60 mg/kg/day orally. The systolic blood pressure was monitored by weekly-measurement of blood pressure by non-invasive tail cuff technique. The effect on endothelial dysfunction was estimated pharmacologically by vascular reactivity studies on isolated aortic rings in vitro. Histopathological examination of the heart using hematoxylin and eosin and Masson trichrome stain was done to assess the degree of myocardial fibrosis. Coagulation profile was assessed by the bleeding time test and the prothrombin time. Our study revealed that both lisinopril and ramipril decreased the systolic blood pressure significantly compared to L - NAME with insignificant difference between them in all measurements. Ramipril showed marked improvement of endothelial reactivity and cardiac fibrosis compared to lisinopril. Pronounced prolongation in bleeding time and prothrombin time with the tissue ACEI ramipril and its combination with aspirin compared with the plasma ACEI lisinopril