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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. Experiments were performed to identify the effects of oleanolic acid on the renin-angiotensin system and cardiac natriuretic hormone (ANP) system, and also renal function and blood pressure in normotensive and renovascular hypertensive rats. The change in the plasma levels of hormones and the expressions of renin, angiotensin II receptors, ANP, natriuretic peptide receptor-C, M 2 muscarinic receptor and GIRK4 were determined in the kidney, heart and aorta. Oleanolic acid was administered orally for 1 or 3 weeks. Here, we found that oleanolic acid suppressed plasma levels of renin activity and aldosterone and intrarenal levels of renin and angiotensin II type 1 receptor expression and increased angiotensin II type 2 receptor in normotensive and hypertensive rats. Also, oleanolic acid increased plasma levels of ANP. Further, oleanolic acid suppressed angiotensin II type 1 receptor and natriuretic peptide receptor-C expression and increased angiotensin II type 2 receptor and ANP expression in the heart and aorta. Along with these changes, oleanolic acid accentuated urinary volume, electrolyte excretion and glomerular filtration rate in normotensive rats and suppressed arterial blood pressure in hypertensive rats. These findings suggest that beneficial effects of oleanolic acid on the cardiorenal system are closely associated with its roles on the renin-angiotensin system and cardiac natriuretic hormone system. [ABSTRACT FROM AUTHOR]

Weaning preeclamptic (PE) rats exhibit exaggerated endotoxic signs of hypotension and cardiac autonomic neuropathy. Considering the role of renin-angiotensin system (RAS) in maternal programming during PE, we investigated the hypothesis that gestational modulation of offensive (Angiotensin II, Ang II) and defensive (Ang 1–7) components of RAS alleviates cardiovascular hyperresponsiveness of weaning PE mothers to postpartum endotoxemia. PE was induced by treating pregnant rats with the nitric oxide synthase inhibitor L-NAME (50 mg/kg/day) for 7 consecutive days starting from gestational day 14. The PE-associated elevations in gestational systolic blood pressure and proteinuria were reduced after gestational treatment with Ang 1–7 (Ang II-derived vasodilator), losartan (AT1 receptor antagonist), pioglitazone (RAS modulator), or combined losartan/pioglitazone, with the latter therapy being the most effective. In weaning PE rats, the potentiated falls in mean arterial pressure and spectral index of cardiac sympathovagal balance (low frequency/high frequency ratio) caused by i.v. Lipopolysaccharides (LPS, 5 mg/kg) were attenuated by all therapies. Pioglitazone and Ang 1–7 were more effective in reversing increases and decreases in left ventricular contractility and isovolumic relaxation time constant, respectively, seen in endotoxic PE mothers. Immunohistochemically, cardiac Toll-like receptor 4 (TLR-4) expression was increased in endotoxic PE rats, and this effect was abrogated by Ang 1–7 or losartan/pioglitazone. The same treatments blunted the increased cardiac angiotensin converting enzyme (ACE) expression whereas ACE2 expression was altered by none of the intervening therapies. Overall, the mitigation of Ang II/ACE imbalances alleviates the sensitized cardiovascular and inflammatory actions of endotoxemia in weaning PE mothers. • Prenatal losartan/pioglitazone regimen reduces PE hypertension and proteinuria. • Endotoxic hypotension in PE rats is attenuated by Ang1-7 and RAS inhibitions. • Ang1-7 or RAS inhibition blunts endotoxic cardiac parasympathetic dominance. • Ang 1–7 normalizes PE/LPS-evoked tachycardia and diastolic dysfunction. • Cardiac TLR-4/ACE protein expressions are abrogated by Ang1-7 or RAS inhibition. [ABSTRACT FROM AUTHOR]