| Background Previous studies have suggested extensive applications of brain natriuretic peptide(BNP) in cardiovascular diseases.There is increasing evidence showing that BNP is related to atrial fibrillation(AF) and it may be a potential predictor of AF.Both BNP and renin-angiotensin-aldosterone system (RAS) play important roles in AF regulation,but their correlations have not been studied clearly,particularly in blood and cardiac tissue.Objective To study the effect of rapid atrial pacing(RAP) on BNP and RAS, as well as their correlations,furthermore,to analyse the role of BNP in acute AF assessment.Methods Acute AF model was established by implanting electrodes through canine right external jugular vein,RAP group(n=5) received continuous pacing of 400 beats per min(bpm) for 6 hours,while sham group(n=6) underwent no electronic stimulation.Serum BNP,angiotensinⅡ(AngⅡ) and aldosterone(ALD) were tested by enzyme linked immunosorbent assay(ELISA) on 0h,1h,2h,4h and 6h after pacing.At the time point of 6h,samples from free wall of right ventricle(RV) and left ventricle(LV),lateral wall of right atrium(RA) and left atrium(LA) were collected,distribution and expression of BNP in them were observed by immunohistochemical method(IHC) and immunofluorescence. Protein level of BNP was tested by Western Blot.Furthermore,mRNA of BNP, natriuretic peptide receptor-A(NPR-A),natriuretic peptide receptor-b(NPR-B), angiotensinogen(AGT) and angiotensin converting enzyme(ACE) were measured by reverse transcription PCR(RT-PCR).Results The BNP level was significantly increased after RAP in the pacing group(1h:45.3±14.6 pg/ml VS 23.0±6.9 pg/ml;2h:71.5±24.5 pg/ml VS 28.7±13.1 pg/ml;4h:76.5±15.3 pg/ml VS 32.5±8.3 pg/ml;6h:85.7±29.1 pg/ml VS 85.7±29.1 pg/ml,respectively,all P＜0.05 vs.Sham):AngⅡincreased since 2h after pacing(2h:88.6±22.2 pg/ml VS 47.7±11.2 pg/ml:4h:102.18±35.8 pg/ml VS 46.1±15.7 pg/ml;6h:104.94±13.6 pg/ml VS 47.1±21.2 pg/ml,respectively, P＜0.01 vs.Sham).Regression analysis revealed a positive correlation between Serum BNP and AngⅡ(r=0.737,P＜0.01 vs.Sham).Serum ALD showed no obvious changes in 6h after RAP.IHC and immunofluorescence observation showed BNP positive grains and some focal aggregation in intracytoplasm.After RAP,the intensity of positive dyeing turned to be more intensive in atrium and ventricle,especially in right atrium.Significant difference was noted in the desity of positive BNP dots(0.61±0.06 VS 0.29±0.13;0.47±0.09 VS 0.32±0.11,both P＜0.05 vs Sham).Western Blot showed that RAP group had higher atrial and ventricular BNP levels than sham group(P＜0.05).RAP group had decreased LV BNP mRNA(P＜0.05 vs.Sham) and increased BNP mRNA in RV and RA; NPR-A mRNA downregulated in ventricles(P＜0.01 vs.Sham) while significant NPR-B mRNA upregulation was observed in cardiocyte(LV P＜0.01 vs.Sham, atria and RV P＜0.05 vs.Sham);significant AGT mRNA expression was observed only in RA(P＜0.01 vs.Sham);ACE mRNA downregulated in LA and LV(P＜0.05 vs.Sham,P＜0.01 vs.Sham),while it increased both in RA and RV(P＜0.01 vs.Sham,P＜0.05 vs.Sham).Conclusion Short-term RAP results in rapid changes of BNP in blood and myocardium tissue,and there is parallel expression of AGT mRNA,ACE mRNA and BNP mRNA in right atrium.There may be a relationship between BNP and AngⅡindicating BNP and RAS act as autocrine or paracrine secretion factors in local tissue regulation except for its neruocrine functions.BNP may be a useful predictor of acute AF. |
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