Oleanolic acid prevents increase in blood pressure and nephrotoxicity in nitric oxide dependent type of hypertension in rats

Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear. Objective: To explore antihypertensive activity of OA in N-w-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA. Materials and Methods: Five groups of rats were investigated as normal control, L-NAME (40 mg/kg/day), L-NAME enalapril (15 mg/kg/day), L-NAME l-arginine (100 mg/kg/day), and L-NAME OA (60 mg/kg/day) for 4 weeks. The systolic blood pressure, body weight, and heart rate were measured weekly for 4 weeks. Serum nitrate/nitrite (NOx) level, urine electrolytes concentration, cardiac mass index, and serum creatinine level were determined followed by organ histopathology. Results: OA and enalapril delayed the rise in blood pleasure following L-NAME administration. Decreased serum NOx level was not significantly increased with any of the treatment. OA produced a small, though nonsignificant, increase in the NOx level. L-NAME administration did not affect cardiac mass index. There was an increase in serum creatinine upon L-NAME administration which was prevented by OA. Decreased urine volume, urine sodium and potassium were reversed by OA. Conclusion: These results suggest that the antihypertensive effect of OA in L-NAME hypertension is due to diuresis and nephroprotection. However, OA has nonsignificantly affected the NO levels.