Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

Abstract

BackgroundMyocardial ischemia and reperfusion lead to impairment of electrolyte balance and, eventually, lethal arrhythmias. The aim of this study was to investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II) production on heart tissue with ischemia-reperfusion damage, arrhythmia, and oxidative stress.Material/MethodsRats were divided into 4 groups: only ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The drugs were given by gavage 30 min before anesthesia. Blood pressure and electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status (TAS), and creatine kinase-MB (CK-MB).ResultsCreatine kinase-MB was not different among the groups. Although TAS was not affected by inhibition of Ang-II production, TOS was significantly lower in the CAP and/or AL groups than in the MI/R group. Furthermore, oxidative stress index was significantly attenuated in the CAP and/or AL groups. Captopril significantly increased the duration of VT during ischemia; however, it did not have any effect on the incidence of arrhythmias. During reperfusion periods, aliskiren and its combinations with captopril significantly reduced the incidence of other types of arrhythmias. Captopril alone had no effect on the incidence of arrhythmias, but significantly increased arrhythmias score and durations of arrhythmias during reperfusion. MAP and heart rate did not show changes in any groups during ischemic and reperfusion periods.ConclusionsAngiotensin-II production appears to be associated with elevated levels of reactive oxygen species, but Ang-II inhibitions increases arrhythmia, mainly by initiating ventricular ectopic beats.

Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41

“…In this study, we have not only confirmed the regulatory role of CAV-1 and ACE2 in Ang II aggravated myocardial I/R injury, but also confirmed the interaction between CAV-1 and ACE2 protein, and clarified a new mechanism that Ang II aggravates myocardial I/R injury, providing a potential target for treating myocardial I/R injury. Meanwhile, some studies have found that inhibition of Ang II production increases susceptibility to acute ischemia/reperfusion arrhythmias [49]. Therefore, regulating Ang II at a relatively stable level is essential for the prevention and treatment of myocardial I/R injury.…”

Renin–Angiotensin System Antagonism Protects the Diabetic Heart from Ischemia/Reperfusion Injury in Variable Hyperglycemia Duration Settings by a Glucose Transporter Type 4-Mediated Pathway

“…The renin–angiotensin system (RAS) plays a pivotal role in combating myocardial diseases and might ultimately participate in the aggravation of reperfusion injury [ 17 ]. Although RASblockers are beneficial during myocardial ischemia, its effects on the diabetic myocardium remain controversial [ 18 , 19 ].…”

Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury

“…For patients with myocardial infarction, timely myocardial reperfusion therapy has become the main strategy for myocardial salvage [1] . However, reperfusion can further exacerbate myocardial ischemia/reperfusion (I/R) injury, which can cause reperfusion arrhythmia [2] . Therefore, intensive research has focused on the pathophysiological mechanisms related to reperfusion arrhythmia and the development of potential therapeutic strategies.…”