LAUSR

HIGHLIGHTSNaHS and Na2S augmented high stretch‐induced ANP secretion whereas GYY4137 and sodium thiosulfate did not.NaHS‐stimulated ANP secretion was blocked by the pretreatment with inhibitor for KATP channel, NOS, sGC, PI3K or protein kinase B.The attenuation of NaHS‐induced ANP secretion in ISP‐treated rat atria may be due to the low expression of eNOS protein.These findings clarify that NaHS stimulates ANP secretion through the KATP channel and PI3K/Akt/NOS/sGC pathway. ABSTRACT Hydrogen sulfide (H2S) is normally produced from l‐cysteine in mammalian tissues and related to the pathogenesis of cardiovascular diseases. The aim of this study is to investigate the effects of H2S donor on atrial natriuretic peptide (ANP) secretion and define its mechanism using normal and isoproterenol (ISP)‐treated rats. Several H2S donors were perfused into isolated beating rat atria, and atrial pressure (AP) and ANP secretion were measured. NaHS augmented high stretch‐induced ANP secretion and decreased AP in a dose‐dependent manner. The high stretch‐induced ANP secretion was stimulated by Na2S but was not changed by GYY4137 and sodium thiosulfate. NaHS and Na2S produced very high amount of H2S rapidly whereas GYY4137 produced very low amount of H2S slowly. NaHS‐stimulated ANP secretion was blocked by the pretreatment with inhibitor for KATP channel, nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC), phosphoinositol 3 kinase (PI3K) or protein kinase B. H2S synthesis enzyme inhibitor (DL‐propargylglycine) did not show any significant changes in atrial parameters. However, the response of ANP secretion to NaHS markedly attenuated and DL‐propargylglycine 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 &ggr;‐lyase, was not changed in ISP‐treated rat atria. The attenuation of NaHS‐induced ANP secretion in ISP‐treated rat atria may be due to the low expression of eNOS protein. These findings clarify that NaHS stimulates ANP secretion via the KATP channel and the PI3K/Akt/NOS/sGC pathway in rat atria.