Gallic acid increases atrial natriuretic peptide secretion and mechanical dynamics through activation of PKC

Aims Gallic acid (GA) protects against myocardial ischemia-reperfusion (I/R) injury, prevents cardiac hypertrophy and fibrosis, and has anti-inflammatory activity in the heart. However, its effects in regulating atrial natriuretic peptide (ANP) secretion are unknown. The aim of this study was to determine the function of GA in regulating ANP secretion and atrial dynamics in rat atria. Key findings GA (0.01, 0.05, and 0.1 μmol/L) significantly increased atrial ANP secretion and induced positive inotropy dose-dependently. GA (0.1 μmol/L) also increased plasma level of ANP and hemodynamics in rats. These effects were accompanied by upregulation of atrial protein kinase C subtypes β and e (PKC β and PKC e ), which was completely blocked by LY333531 and EAVSLKPT, antagonists of protein PKC β and PKC e , respectively. GA-induced ANP secretion was also attenuated by Go6983 but not rottlerin, antagonists of PKC α and PKC δ , and the positive inotropy was reversed by Go6983. U-73122, a phospholipase C (PLC) antagonist, mitigated the effects of GA on ANP secretion and mechanical dynamics and downregulated Phospho-PLC β at Ser 537 (pPLC β S537), Phospho-PLC β at Ser 1105 (pPLC β S1105), PKC β and PKC e levels, whereas KN62, an inhibitor of Ca 2 + /calmodulin-dependent kinase II, was not modified the GA-induced ANP secretion and suppressed GA-induced mechanical dynamics. Significance GA promotes ANP secretion and effects positive inotropy with regard to mechanical dynamics through the activation of PLC-PKC signaling in rat atria.