Department of Physiology, Research Institute for Endocrine Sciences, Chonbuk National University Medical School, Jeonju 54907, Republic of Korea.
Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Peptides. 2019 Jan;111:89-97. doi: 10.1016/j.peptides.2018.04.005. Epub 2018 Apr 21.
Hydrogen sulfide (HS) 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 HS donor on atrial natriuretic peptide (ANP) secretion and define its mechanism using normal and isoproterenol (ISP)-treated rats. Several HS 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 NaS but was not changed by GYY4137 and sodium thiosulfate. NaHS and NaS produced very high amount of HS rapidly whereas GYY4137 produced very low amount of HS slowly. NaHS-stimulated ANP secretion was blocked by the pretreatment with inhibitor for K channel, nitric oxide synthase (NOS), soluble guanylyl cyclase (sGC), phosphoinositol 3 kinase (PI3K) or protein kinase B. HS 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 HS 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 channel and the PI3K/Akt/NOS/sGC pathway in rat atria.
硫化氢 (HS) 通常在哺乳动物组织中由 l-半胱氨酸产生，并与心血管疾病的发病机制有关。本研究旨在使用正常和异丙肾上腺素 (ISP) 处理的大鼠研究 HS 供体对心房利钠肽 (ANP) 分泌的影响，并确定其机制。将几种 HS 供体灌注到分离的跳动大鼠心房，测量心房压力 (AP) 和 ANP 分泌。NaHS 以剂量依赖性方式增强高拉伸诱导的 ANP 分泌并降低 AP。NaS 刺激高拉伸诱导的 ANP 分泌，但 GYY4137 和硫代硫酸钠不改变其分泌。NaHS 和 NaS 迅速产生大量 HS，而 GYY4137 则缓慢产生少量 HS。NaHS 刺激的 ANP 分泌被 K 通道抑制剂、一氧化氮合酶 (NOS)、可溶性鸟苷酸环化酶 (sGC)、磷酸肌醇 3 激酶 (PI3K) 或蛋白激酶 B 的预处理所阻断。HS 合成酶抑制剂 (DL-丙炔基甘氨酸) 对心房参数没有显示出任何显著变化。然而，NaHS 对 ANP 分泌的反应在 ISP 处理的大鼠心房中明显减弱，并且 DL-丙炔基甘氨酸抑制了 ISP 处理的大鼠心房中的 ANP 分泌。eNOS 蛋白的表达减少，但 ISP 处理的大鼠心房中肌细胞特异性 HS 产生酶胱硫醚 γ-裂合酶的表达没有改变。NaHS 诱导的 ANP 分泌在 ISP 处理的大鼠心房中的衰减可能是由于 eNOS 蛋白的低表达所致。这些发现阐明了 NaHS 通过大鼠心房中的 K 通道和 PI3K/Akt/NOS/sGC 途径刺激 ANP 分泌。
