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

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DOI: 10.4236/jbm.2017.51001    517 Downloads   610 Views  

ABSTRACT

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.

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Guan, C. , Jia, Y. , Bian, C. , Zhang, B. , Ding, D. and Cui, X. (2017) Forskolin Modulates the Inhibitory Effect of C-Type Natriuretic Peptide on Hypoxia-Induced Atrial Dynamics and Hypoxia Inducible Factor 1 Alpha Activity. Journal of Biosciences and Medicines, 5, 1-10. doi: 10.4236/jbm.2017.51001.

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