Study Of Impacts And Mechanisms Of Renal Denervation On Cardiac Dysfunction In Models With Chronic Pressure Overload

Objective: To investigate the impacts and mechanisms of renal denervation(RDN)on chronic cardiac dysfunction,cardiovascular remodeling and neurohumoral response in SD rats with chronic pressure overload induced by transverse aortic constriction(TAC).Methods: 50 SD male rats were randomly assigned to three groups: RDN(TAC + RDN,n=20);Sham(TAC + Sham RDN,n=20);and Control [Sham(TAC+RDN),n=10].TAC and RDN(or sham operations)were carried out at week 0(baseline)and week 6,respectively.Echocardiography was performed at week 0,6,10,14.Indices of hemodynamics mainly included ejection fraction(EF),fractional shortening(FS),left atrial diameter(LAD),interventricular septal thickness(IVSTd)and left ventricular posterior wall in diastole(LVPWd),left ventricular mass index(LVMI),systolic blood pressure(SBP).Survival over the 14-week experiment was analyzed according to the daily recording of deaths by the standard Kaplan-Meier analysis with the log rank test.The myocardial fibrosis,aortic remodeling was evaluated by Masson staining and hypertrophy remodeling were evaluated by HE staining.The protein expressions of myocardial ? adrenergic receptor(?-AR),Ca2+ ATPase in the cardiac sarcoplasmatic reticulum(SERCA),and angiotensin II type 1 receptor(AT1R)were detected by Western Blot.Enzyme linked immunosorbent assay(ELISA)was used to measure changes of plasma B-type natriuretic peptide(BNP),norepinephrine(NE),angiotensin II(Ang II)and arginine vasopressin(AVP).Results: Six weeks after TAC,EF [(70.9±1.8)%?(70.2±1.7)% vs.(78.7±2.3)%,P<0.05] and FS [(41.8±1.6)%?(41.3±1.3)% vs.(49.1±2.4)%,P<0.05] of rats in RDN and Sham groups were decreased whlie LAD [(4.90±0.25)mm?(4.99±0.28)mm vs.(3.83±0.17)mm,P<0.05] and LVMI[(2.47±0.11)mg/g ?(2.60±0.16)mg/g vs.(1.97±0.05)mg/g,P<0.05] were increased significantly than Control rats.Echocardiography at week 10(4 weeks after RDN)showed that LAD,IVSTd and LVPWd were significantly improved in RDN than Sham rats [(4.58±0.26)mm vs.(5.83±0.35)mm,(2.00±0.04)mm vs.(2.26±0.08)mm,(2.07±0.05)mm vs.(2.33±0.08)mm.P<0.05,respectively].But the LAD,IVSTd and LVPWd at week 14(8 weeks after RDN)were improved without significance compared with Sham animals.Myocardial fibrosis,levels of plasma BNP,Ang II,NE and AVP were improved in RDN than Sham rats [(1.78±0.1)% vs.(2.92±0.3)%,(158.38±8.64)pg/ml vs.(219.08±29.2)pg/ml,(98.92±7.66)pg/ml vs.(181.4±14.24)pg/ml,(196.52±40.89)pg/ml vs.(350.76±50.76)pg/ml,(3.59±0.63)pg/ml vs.(7.65±1.52)pg/ml.P<0.05,respectively].The protein expressions of myocardial ?-AR [?1AR:(1.05±0.1)vs.(0.58±0.07),?2AR:(0.89±0.06)vs.(0.55±0.03),SERCA(1.36±0.01)vs.(0.84 ±0.03).P<0.05,respectively] were up-regulated in RDN than Sham rats.The AT1 R expression in myocardium was down-regulated.[(1.19±0.11)vs.(1.64±0.09);P<0.05 ].Compared with rats in RDN group,media thickness of aorta was thinner,lumen diameter of aorta was enlarged in Sham rats.The M/L ratio(media thickness/lumen diameter of aorta,M/L)was improved in RDN than Sham rats.Conclusion: RDN attenuates the left atrial enlargement,left ventricular hypertrophy,myocardial fibrosis and aortic dilatation.It delays the transformation of cardiac function status from compensatory hypertrophy to decompensated dilatation in TAC rats with chronic pressure overload.The mechanisms may involve the up-regulating of myocardial ?-AR and SERC A expressions,down-regulating of AT1 R expression,decreasing levels of plasma BNP,Ang II,NE and AVP in TAC rats with cardiac dysfunction induced by chronic pressure overload.