Preventive Effects of the Angiotensin-II Receptor Blocker on Atrial Remodeling in an Ischemic Heart Failure Model of Rats

Abstract

Background and ObjectivesIt is widely known that angiotensin-II receptor blockers (ARBs) have reverse remodeling effects in atrium. Although atrial fibrillation is frequent in ischemic heart failure clinically, experiments to demonstrate ARB's effects on atrial remodeling in a heart failure model are rare.Materials and MethodsA heart failure model and a sham-operated group were formed in 25 Sprague-Dawley male rats of roughly 260 g in weight. Ischemic heart failure models were obtained via ligation of the left anterior descending coronary artery. In the ARB group, 30 mg/kg of losartan was administrated over a day for 4 weeks. Echocardiography was performed to measure left ventricle ejection fraction and left atrial diameter (LAD) at the baseline and 4 weeks after the operation. 4 weeks later, histologic and immunohistochemical evaluation were performed.ResultsGroups were divided into the sham group, heart failure group, and heart failure-ARB group. We maintained 5 rats in each group for 4 weeks after operation. The decrease of left ventricular ejection fraction in the heart failure-ARB group was less than that in the heart failure group (p=0.023). The increase of LAD in the heart failure-ARB group was less than that in the heart failure group (p=0.025). Masson's trichrome stain revealed less fibrosis in the heart failure-ARB group. Immunohistochemical stain and western blot for connexin 43 showed less expression in the heart failure-ARB group.ConclusionIn the ischemic heart failure model of rats, structurally and histologically, the ARB, losartan, has atrial reverse-remodeling effects. However, electrically, its role as an electrical stabilizer should be studied further.

A New Chimeric Natriuretic Peptide, CNAAC, for the Treatment of Left Ventricular Dysfunction after Myocardial Infarction

“…Cardiac dysfunction and pathophysiologic adaption were observed in rats subjected to ligation of the coronary artery 17 , 18 . In the current study, the left ventricular dysfunction model was established via ligation of the coronary artery for 4 weeks.…”

Angiotensin‐receptor blocker losartan alleviates atrial fibrillation in rats by downregulating frizzled 8 and inhibiting the activation of WNT‐5A pathway

“…All rats were assigned to 6 groups, with 12 rats per group. (a) model group (AF); (b) sham group; (c) AF + ARB group: after modelling, rats were given 30 mg/kg ARB Cozaar (losartan kalium; Merk Sharp and Dohme) by gavage every day for 4 weeks 13 ; (d) AF + S group: after modelling, rats were given drinking water by gavage instead of ARB; (e) AF + ARB + oe‐FZD8 group: after modelling, rats were treated with ARB and injected once with pcDNA3.1 FZD8 overexpression plasmids (oe‐FZD8) through the tail vein; (f) AF + ARB + oe‐negative control (NC) group: after modelling, rats were treated with ARB and injected once with oe‐NC plasmids through the tail vein. oe‐FZD8 and oe‐NC plasmids were designed and tested by Bio‐scientific Company and were used in the experiment according to the instructions.…”

“…Angiotensin-receptor blocker (ARB) is a representative antihypertensive drug, which has the reverse remodelling functions in the atrium and plays a role in AF. 13 AF is related to atria progressive structural and electrical remodelling, and ARB and related mediators are centrally involved in atrial fibrosis. 14 Septal defect affects left atrial function and increases the risk of AF recurrence, whereas angiotensin-converting enzyme inhibitor/ ARB can reduce septal defect.…”

“…Angiotensin‐receptor blocker (ARB) is a representative antihypertensive drug, which has the reverse remodelling functions in the atrium and plays a role in AF 13 . AF is related to atria progressive structural and electrical remodelling, and ARB and related mediators are centrally involved in atrial fibrosis 14 .…”