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

AimsGallic 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 findingsGA (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 ε (PKCβ and PKCε), which was completely blocked by LY333531 and EAVSLKPT, antagonists of protein PKCβ and PKCε, respectively. GA-induced ANP secretion was also attenuated by Gö6983 but not rottlerin, antagonists of PKCα and PKCδ, and the positive inotropy was reversed by Gö6983. U-73122, a phospholipase C (PLC) antagonist, mitigated the effects of GA on ANP secretion and mechanical dynamics and downregulated Phospho-PLCβ at Ser537 (pPLCβ S537), Phospho-PLCβ at Ser1105 (pPLCβ S1105), PKCβ and PKCε levels, whereas KN62, an inhibitor of Ca2 +/calmodulin-dependent kinase II, was not modified the GA-induced ANP secretion and suppressed GA-induced mechanical dynamics.SignificanceGA promotes ANP secretion and effects positive inotropy with regard to mechanical dynamics through the activation of PLC-PKC signaling in rat atria.