Effects Of Endoplasmic Reticulum Stress On The Secretion Of Anp By Rapid Atrial Pacing Induced Atrial Fibrillation

Background and Objectives:Atrial natriuretic peptide(atrial natriuretic peptide,ANP)is involved in the peptide hormones,blood pressure and body fluid regulation,mainly by the synthesis and release of atrial muscle.Atrial fibrillation,the plasma concentration of ANP increased,and ANP concentration and duration of atrial fibrillation.Atrial fibrillation is the endoplasmic reticulum stress(endoplasmic reticulum,stress,ERS),but the ERS of the ANP regulation mechanism of abnormal secretion of atrial fibrillation is not clear.In this study,rapid atrial pacing in rabbits as the research object,to explore the regulatory effect of ERS on the secretion of atrial ANP,pathophysiological mechanisms of cardiac endocrine characteristics so as to clarify the changes in atrial fibrillation,and provide experimental basis for clinical prevention and treatment of atrial fibrillation.Methods:New Zealand white rabbits(2.5 ± 0.5kg)that builded rapid atrial pacing model in vivo and isolated perfused beating atria model were used to experiment.(1)Rapid atrial pacing rabbit models in vivo:divided into control group,stimulation group.Using BL-420 physiological signal acquisition system tostimulate the rabbit atrial through right external jugular vein catheterization,meanwhile record limb-lead ECG on surface;atrial morphological changes were observed by HE staining after rapid pacing for 2 hours,and using transmission electron microscopy to observe atrial endoplasmic reticulum ultrastructural changes after rapid pacing for 2 hours;in addition,expression of ERS marker protein GRP78 was assayed by western blot,blood ANP concentration was detected by radioimmunoassay,to discuss the relations between rapid atrial pacing and the secretion of ERS and ANP.(2)Isolated perfused beating atria model:separating normal rabbits left atrium,HEPES buffer perfused atrium for 60 min,after stabilization,began collecting a perfusion fluid tube every 2 min,a total of 36 tubes.the former 24 tubes collected control group,the latter 12 tubes collected tunicamycin induced ERS group,meanwhile record stroke volume and atrial pressure.Measure the concentration of ANP in the perfusion by using radioimmunoassay.Results:1.The use of the external jugular vein catheterization-induced rapid atrial pacing,successfully simulated the occurrence of atrial fibrillation;2.HE observed:atrial muscle fibers were elongated,branched which connected into a network,and the light and dark stripes were visible.Now oval nuclei,lay the central of atrial fibers,compared with the sham operation group,the group of cardiac pacing for 2 hours had no significant change;TEM results:atrial sarcoplasmic reticulum after pace 2 hours expended,formed a large number of vacuoles,glycogen particles aggregated significantly,the connection gap widened,myofilament dissolved;3 Changes were measured by Western blot GRP78 in atrial tissues:the group of atrial pacing 2h GRP78 expression was significantly increased in tissues comparing with the control group;ANP concentration in blood was measured by radioimmunoassay,In the control group:0.958±0.122?g/L,pacing 2h group:2.011±0.186?g/L;4 tunicamycin increased significantly ANP secretion in isolated perfused atria beat,but atrial stroke volume and internal pressure had no significant differences comparing with the control group.Conclusion:These findings indicate that endoplasmic reticulum stress has important role in the regulation of atrial ANP secretion.The present study also shows that ERS in the regulation of atrial ANP release is involed in the atrial fibrillation.