Foskolin Modulates The Inhibitory Effect Of C-type Natriuretic Peptide On Hypoxia-indced Atrial Dynamics And Hypoxia Inducible Fctora-1 Alpha Activity

Aim:Our study investigated the effects of C-type natriuretic peptide(CNP)on atrial dynamics and hypoxia inducible factor 1 alpha(HIF-1a)activity,and explored the effect of forskolin on the regulation of hypoxia atrial mechanical activity and HIF-1a activity by CNP,in perfused beating rat atria,under hypoxic conditions.Methods:In this study,SD rats were used as experimental subjects to prepare isolated perfused acute hypoxic atrial model.The experiment was divided into control group,hypoxia group,hypoxia plus CNP group,hypoxia plus forskolin group,hypoxia plus CNP group plus forskolin group.Using a biofilter recorded the changes of atrial beat pressure.The protein levels of phosphodiesterase subtype 3A(PDE 3A)protein and HIF-1a protein were determined by Western blot.Results:1.Hypoxia obviously inhibited atrial beat pressure,CNP also substantially induced inhibition of atrial mechanical activity in the hypoxic atria.2.Forskolin significantly attenuated the inhibitory effects of CNP on hypoxia-induced pulse pressure,however,forskolin did not alter the effect of hypoxia alone on atrial pulse pressure.3.Forskolin significantly increased the content of PDE 3 A under hypoxic conditions.Hypoxia alone or hypoxia plus CNP were unable to change the levels of PDE 3A in hypoxia atrial.However,In hypoxic atria CNP significantly reduced the PDE 3 A content in the presence of forskolin。4.Hypoxia alone significantly increased the levels of HIF-1a,and forskolin strengthened the effect of hypoxia on the content of HIF-1;As well as CNP not only can be completely interdicted the hypoxia increased the HIF-1 content of atrial tissue function,but aslo significantly inhibited the effect of forskolin on hypoxia atrial HIF-1 alph a content.Conclusions:1.CNP obviously inhibited atrial dynamics and HIF-la activity in the isolated perfused beating rat atria under hypoxic conditions.2.Forskolin through increased CNP-PDE 3A signaling significantly slows down the inhibitory effect of CNP on atrial mechanical activity and HIF-1 alpha activity.