Losartan Attenuate Myocardial Structure Remodling Of Atrial Fibrillation: Possible Involvement Of Angiotensin-converting Enzyme And Angiotension-converting Enzyme2

Objective: The purpose of this study was to observe the possible involvement ofangiotension-converting enzyme2in AF induced by rapid atrial pacing of the right atriumin dogs, and to evaluate the effects of losartan potassium on atrial electrical remodelingand ACE2. Methods:20healthy mature hibird dogs were grouped randomly as right atrialpacing group (RAP)(n=5), right atrial pacing+losartan potassium small dose (2mg/kg/d)treatment group (n=5) and right atrial pacing+losartan potassium large doses (4mg/kg/d)treatment group (n=5), Sham operated group (n=5).Pacing electrode was Imbedded fromthe external jugular vein to the right atrium. The rapid atrial pacing at600beats perminute was maintained for48hours except control group. Received losartan potassium(2mg/kg/d), losartan potassium (4mg/kg/d) to dogs respectively seven days before rightatrial pacing for Small and Large. Some electrophysiological index were measured,including right atrial effective refractory period (AERP) from different time perod(0hour,pacing6hours, pacing12hours,pacing24hours,pacing36hours,pacing48hours)and different basic pacing cycle length (BCL:300ms,250ms,200ms), frequencyadaptability of AERP, inducibility and duration of induced AF. At the end of theexperiments, the right atrial muscular tissues were detached from the cardic. Relying onthe methods of immunohistochemistry and western blot to measure the expression ofACE2. Results: After pacing48hours,the AERP of right atrial pacing group (RAP) wassignifieantly shortened at different basic pacing cycle length (BCL:300ms,250ms,200ms)(P＜0.05), frequeney adaptability of the AERP was drop, and inducibility and duration ofinduced AF signifieantly increased (P＜0.05)，Losartan could reverse atrial electricalremodeling. The result of immunohistochemical staining and Western blot and radiation immune showed that the expression of ACE2is reduced obviousiy after pacing48hours,losartan potassium can rise ACE2. Conclusion: After pacing dogs48hours, atrialelectrical remodeling were observersed. Furthermore, this study demonstrated that ACE2played an essential role in pacing-induced AF. Losartan could reverse atrial electricalremodeling by regulate expression of ACE2of atrial fibrillation in dogs. Thus, to adjustthe level of ACE2may blockade atrial remodling and provide benefits to patients whosuffered atrial fibrillation.