NaHS Induced ANP Secretion via PI3K/Akt/NO/cGMP and KATP Channel Pathway

Abstract

The third gasotransmitter, hydrogen sulfide (H2S), is related to the pathogenesis of cardiovascular diseases. However, it's still not clear about the relation between H2S and cardiac hormone, atrial natriuretic peptide (ANP). The purpose of this study is to investigate the effects of H2S donor on ANP secretion and seek its mechanism using normal and isoproterenol (ISP)‐treated hypertrophied rat atria. Different doses of H2S donors were perfused into isolated beating rat atria, and atrial pressure and ANP secretion were measured. NaHS (1, 10, 50, 100 μM) augmented high stretch‐induced ANP secretion and decreased systolic atrial pressure (SAP) dose‐dependently. Pretreatment with an inhibitor or antagonist for phosphatidylinositol 3‐kinase (PI3K; wortmannin), protein kinase B (Akt; API‐2), nitric oxide synthase (NOS; L‐NAME), soluble guanylyl cyclase (sGC; ODQ), and KATP channel (glibenclamide) blocked the augmentation of ANP secretion induced by NaHS. The high stretch‐induced ANP secretion was stimulated by Na2S but was not changed by GYY4137 and sodium thiosulfate. H2S synthesis enzyme inhibitor (DL‐propargylglycine, PAG) did not show any significant changes in atrial parameters. However, the response of ANP secretion to NaHS markedly attenuated and PAG suppressed ANP secretion in ISP‐treated rat atria. The expression of eNOS protein was decreased but the expression of cardiomyocyte‐specific H2S producing enzyme, cystathione γ‐lyase, was not changed in ISP‐treated rat ventricles. These findings clarify that NaHS stimulates ANP secretion through PI3K/Akt/NO/cGMP and KATP channel pathway. The modification of ANP secretion by NaHS and H2S synthesis enzyme inhibitor suggests the possible role of endogenous H2S in the pathogenesis of cardiac hypertrophy.Support or Funding InformationSupported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NO 2017‐R1A2B‐4002214).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.