Forskolin Modulates the Inhibitory Effect of C-Type Natriuretic Peptide on Hypoxia-Induced Atrial Dynamics and Hypoxia Inducible Factor 1 Alpha Activity

• 作者: Bo Zhang Chaochao Bian Chengming Guan Dazhi Ding Xun Cui Yanan Jia
• 来源期刊: 生物科学与医学(英文)
• 学科: 医学
• 关键词: C-Type NATRIURETIC Peptide HYPOXIA INDUCIBLE Factor-1α PHOSPHODIESTERASE Adenylyl CYCLASE FORSKOLIN
• 年，卷（期）: swkxyyxyw_2017,（1）
• 页码范围: 1-10
• 页数: 10页
• 分类号: R73

摘要

Our study investigated effects of C-type natriuretic peptide (CNP) on atrial dynamics and hypoxia inducible factor 1 alpha (HIF-1α) activity in perfused beating rat atria, under hypoxic conditions. Hypoxia significantly increased the levels of HIF-1α, concomitant with decreased trial dynamics. CNP (0.1 μmol/L) further decreased atrial dynamics under hypoxia and suppressed hypoxia-induced stimulation of HIF-1α expression. An adenylylcyclase (AC) activator, forskolin (0.1 μmol/L), significantly up-regulated atrial phosphodiesterase subtype 3A (PDE 3A) protein without affecting hypoxia-induced dynamics. In the presence of forskolin, the inhibitory effects of CNP on hypoxia-induced atrial dynamics and HIF-1α levels were significantly attenuated. Forskolin also prevented hypoxia-induced downregulation of PDE3A protein. These findings suggested that CNP inhibited atrial dynamics and HIF-1α activity in the isolated perfused beating rat atria under hypoxic conditions. Furthermore, both effects were modulated by the AC activator forskolin, through activation of CNP-PDE 3A signaling.