Oleanolic acid increases plasma ANP levels via an accentuation of cardiac ANP synthesis and secretion in rats

摘要

Oleanolic acid is known to have beneficial effects on the regulation of cardiovascular homeostasis. The present study was designed to identify the effects of oleanolic acid on plasma levels and atrial synthesis and secretion of atrial natriuretic peptide (ANP). Experiments were performed in rats and isolated perfused beating rat atria. ANP was measured using a selective radioimmunoassay. ANP mRNA expression was measured using real-time quantitative polymerase chain reaction. Administration of oleanolic acid increased plasma ANP levels in a dose-related manner. Similarly, oleanolic acid increased atrial ANP content and ANP mRNA expression. To evaluate the effects of oleanolic acid on ANP secretion, atrial stretch and muscarinic acetylcholine receptor activation were applied to the atria from rats chronically treated with oleanolic acid. Baseline levels of ANP secretion were higher in the atria from rats treated with oleanolic acid compared to rats treated with vehicle. Furthermore, oleanolic acid treatment enhanced the stretch-induced increase in ANP secretion. Acetylcholine in the presence of isoproterenol increased ANP secretion. The acetylcholine-induced increase in ANP secretion was also enhanced in the atria from rats treated with oleanolic acid compared to atria from rats treated with vehicle. The present findings indicate that oleanolic acid increases plasma ANP levels via increased ANP synthesis and secretion in rats. It is proposed that an accentuation of the ANP system is involved in the beneficial effects of oleanolic acid on the regulation of cardiovascular homeostasis.