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Effect of Oleanolic acid on regulation of renal function and hormonal balance in hypertension model

Oleanolic acid is known to possess beneficial effects on the regulation of the cardiovascular homeostasis. However, the exact nature of the role of oleanolic acid on the regulation of body fluid balance and blood pressure homeostasis and its mechanisms involved are not well defined. We hypothesized that oleanolic acid inhibits the renin‐angiotensin system and accentuates renal function. Experiments were performed to identify the effects of oleanolic acid on the renal function, blood pressure, and the renin‐angiotensin system in normotensive and hypertensive rats. Oleanolic acid (0, 20, and 30 mg/kg/day) was administered orally for 1 or 3 weeks. Here, we found that oleanolic acid suppressed the renin‐angiotensin system. Oleanolic acid increased urinary volume, and urinary excretion of Na+, K+, and Cl−, concomitantly with an increase in clearance for creatinine in normotensive rats. Also, oleanolic acid decreased urinary osmolality. Oleanolic acid significantly suppressed arterial blood pressure in renal hypertensive rats. Furthermore, oleanolic acid suppressed plasma levels of renin activity, angiotensin II, aldosterone, and renal renin contents, and gene expressions by real‐time PCR of renin, angiotensin converting enzyme and angiotensin II type 1 receptor in the kidney cortex from normotensive and hypertensive rats. Oleanoliac acid elicited dual effects on the angiotensin II type 2 receptor: suppression with low and accentuation with high dose. These findings suggest that oleanolic acid modulates body fluid and salt balance and blood pressure homeostasis by suppressing the systemic and intrarenal renin‐angiotensin system.