ABSTRACT
In this study, we compare between the renoprotective effects of curative and prophylactic doses of carvedilol and lisinopril in L-NAME treated rats. Rats were classified into seven groups: the first and second (normal control and hypertensive control) groups received distilled water and L-NAME (L-nitro argentine methyl ester, 50 mg/kg per day), respectively, for eight weeks. The third and fourth groups received L–NAME (50mg/kg per day) plus a prophylactic dose of carvedilol (15mg/kg per day) or lisinopril (20mg/kg per day), respectively, for eight weeks. The fifth, sixth and seventh groups received L-NAME (50mg/kg per day) for eight weeks, followed by curative doses of carvedilol (30mg/kg per day), lisinopril (40mg/kg per day) or carvedilol (15mg/kg per day) plus lisinopril (20mg/kg per day), respectively, for five weeks. The drugs were administered by gastric gavage. During prophylactic therapy, carvedilol and lisinopril decreased L-NAME induced rise in systolic blood pressure (SBP) and serum creatinine levels. Furthermore, both drugs improved microalbuminuria and renal histopathological changes and increased serum nitric oxide (sNO). During curative therapy, carvedilol improved microalbuminuria and renal histopathological changes. lisinopril or the combination of carvedilol and lisinopril improved all L-NAME induced changes. The combination improved renal histopathological changes more significantly than each individual drug.
In conclusion, carvedilol and lisinopril have prophylactic and curative renoprotective effects in L-NAME treated rats. Carvedilol has similar effectiveness as the converting enzyme inhibitor, lisinopril, in reducing the hypertension, proteinuria and glomerulosclerosis associated with L-NAME induced chronic hypertensive renal failure in rats making chronic renal disease as a therapeutic target for this drug. Moreover, a combination of both drugs at half the therapeutic doses significantly ameliorates hypertension-induced renal damage and improves renal functions, indicating the role of this low-dose combination as an effective therapeutic option if a multi-anti-hypertensive regimen is desirable.
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