Effects of acute angiotensin II on ischemia reperfusion injury following myocardial infarction

Abstract

Myocardial infarction (MI) induces cardiac remodeling. This may increase the susceptibility of the infarcted heart to subsequent ischemic events. While chronic angiotensin II blockade is cardioprotective post-MI, the acute effects of angiotensin II in ischemia-reperfusion injury (IR) remains unclear. In the present study, we tested whether angiotensin II administration altered recovery of left ventricular (LV) function to IR in hearts from sham and MI rats. Echocardiography, LV pressure-volume relationships, and IR performance were established in subsets of sham (N = 27) and MI hearts (N = 41). IR was conducted in red-cell-perfused Langendorff hearts (60 minutes of low-flow ischemia; 30 minutes of reperfusion) during vehicle or angiotensin II infusions (10−7 M). MI hearts were dilated and had reduced fractional shortening and blunted systolic elastance (p < 0.05). Despite systolic dysfunction in MI, functional recovery to IR was similar to sham. Angiotensin II significantly worsened IR performance in sham (p < 0.05), but not MI. The effect of angiotensin II on in vitro cardiomyocyte survival under various pH conditions was also tested. Acidosis increased cardiomyocyte death and angiotensin II potentiated this effect. We conclude that IR performance is similar between sham and MI hearts and that MI hearts are resistant to angiotensin II-induced cardiac dysfunction in response to IR.

Comparison of the effects of losartan, captopril, angiotensin II type 2 receptor agonist compound 21, and MAS receptor agonist AVE 0991 on myocardial ischemia–reperfusion necrosis in rats

“…The number of AT 1 receptors in the heart has been shown to increase after myocardial ischemia [45]. It has been shown in many studies that the inhibition of the AT 1 receptor using ARB does not suppress the vascular functions induced by the stimulation of the AT 2 receptor [46‐48].…”

Heart‑lung crosstalk in pulmonary arterial hypertension following myocardial infarction (Review)

“…Increased expression of AT1R and AT2R has been demonstrated in cMs in non-infarcted areas following MI. In vitro, acidosis promotes death of cMs and AngII enhances this effect (18). There is increasing evidence that AngII induces apoptosis of lung parenchymal cells, causing pulmonary vascular remodeling that ultimately leads to PAH, and that it also induces hypertrophy of CMs, inflammation and fibrosis during cardiac ischemic injury.…”

“…It has been established that RAS is activated by a decline in cardiac function after MI, and that PAH is caused by both mechanical pressure and contraction mediated by AngII and vascular remodeling. The resultant further impairment of cardiac function in turn promotes the development of PAH (18,20). The initiation and development of chronic PAH originate from pulmonary vascular Ec dysfunction.…”

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy

“…A wealth of evidence suggests that the renin-angiotensin system (RAS) plays an important role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury (Mann et al, 2015;Donnarumma et al, 2016). Angiotensin II (Ang II) is upregulated after myocardial I/R and aggravates myocardial injury mediated by Ang II type 1 (AT 1 ) receptor (Mann et al, 2015).…”