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(ω)-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.

Effect of Viscum articulatum Burm. (Loranthaceae) in Nω-nitro-L-arginine methyl ester induced hypertension and renal dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum articulatum Burm. is used traditionally in Chinese medicine for treating hypertension. AIM OF THE STUDY: The present study was designed to evaluate the antihypertensive activity of the methanolic extract of Viscum articulatum (MVA) against N(ω)-nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats. MATERIALS AND METHODS: Six groups of rats were investigated for 4 weeks as normal control, L-NAME (40 mg/kg/day), L-NAME+enalapril (15 mg/kg/day), L-NAME+L-arginine (100 mg/kg/day), L-NAME+MVA (200 mg/kg/day) and L-NAME+MVA (400 mg/kg/day) for four weeks. The systolic blood pressure (SBP) and heart rate (HR) were measured weekly throughout the experimental period. The urine electrolytes concentration, cardiac mass index, serum nitrate/nitrite (NO(x)) level, serum creatinine level and lipid profile were determined. RESULTS: Treatment with MVA (200 and 400 mg/kg) or enalapril delayed the rise in SBP produced by administration of L-NAME. None of the treatments had a significant effect on the depression of the serum NO(x) level caused by L-NAME. The serum creatinine and total cholesterol concentrations were elevated upon administration of L-NAME, and this elevation was prevented by MVA co-administration. The urine volume and urine potassium ion level were depressed by L-NAME administration and this effect being inhibited in MVA and enalapril groups. There was no cardiac hypertrophy and HR change after 28 day of L-NAME administration. CONCLUSION: We conclude that MVA may have an antihypertensive effect in the NO deficient type of hypertension, which may be attributed to its diuretic, nephroprotective and hypolipidemic actions.

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 µg/kg/day s.c.) or saline (vehicle) for 10 days. In a prevention study, the rats received oleanolic acid (60 mg/kg i.p.) for 5 days, followed by dexamethasone or saline for 10 days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60 mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p < 0.01 and p < 0.05, respectively) without showing any significant effect on the dexamethasone-induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p < 0.05). These findings suggest that oleanolic acid (60 mg/kg i.p.) prevents dexamethasone-induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action.