Hydrogen sulfide donor, NaHS, stimulates ANP secretion via the KATP channel and the NOS/sGC pathway in rat atria

Abstract Hydrogen sulfide (H 2 S) 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 H 2 S donor on atrial natriuretic peptide (ANP) secretion and define its mechanism using normal and isoproterenol (ISP)-treated rats. Several H 2 S 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 Na 2 S but was not changed by GYY4137 and sodium thiosulfate. NaHS and Na 2 S produced very high amount of H 2 S rapidly whereas GYY4137 produced very low amount of H 2 S slowly. NaHS-stimulated ANP secretion was blocked by the pretreatment with inhibitor for K ATP channel, nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC), phosphoinositol 3 kinase (PI3K) or protein kinase B. H 2 S 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 H 2 S producing enzyme, cystathione γ-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 K ATP channel and the PI3K/Akt/NOS/sGC pathway in rat atria.