Abstract
Hypoxia induces myocardial injury through the activation of inflammatory and oxidative processes. The pivotal role of the renin angiotensin system (RAS) in the pathogenesis of cardiovascular diseases has been firmly established in clinical trials and practice; in fact many experimental and clinical data have highlighted that its inhibition has a cardioprotective role. Activated RAS also stimulates inflammation directly inducing proinflammatory and oxidative gene expression. This study aimed to investigate the protective role of a pre-treatment (10 and 100 μM) with irbesartan on injury induced by 24 h of hypoxia in HL-1 cardiomyocytes; in particular, we have analyzed the natriuretic peptide (BNP) expression, a biomarker able to modulate inflammatory reaction to cardiac injury and some markers involved in oxidative stress and inflammation. Our results demonstrated that a pre-treatment with 100 μM irbesartan significantly increased SOD activity and catalase expression of 15 and 25%, respectively, compared to hypoxic cells (P<0.05). On the other hand, it was able to reduce the release of peroxynitrite and iNOS protein expression of 20 and 50% respectively (P<0.05). In addition irbesartan exerts an anti-inflammatory activity reducing Toll-like receptors (TLRs)-2 and -4 mRNA expression, TNF-alpha expression and activity (20%) and increasing the expression of the cytokine IL-17 (40%) (P<0.05 vs hypoxia). Our findings also showed that BNP induced by ischemia was significantly and in a concentration-dependent manner reduced by irbesartan. The findings of our study demonstrated that the AT1 receptor antagonist irbesartan exerts a protective role in an in vitro hypoxic condition reducing oxidative stress and inflammation.
Highlights
Myocardial infarction (MI) is one of major cause of death and disability worldwide [1]
In the present study we evaluated the antiinflammatory and antioxidant activity of irbesartan in a murine cellular model, HL-1 cardiomyocytes, exposed to hypoxic stress. For this purpose we investigated the beneficial effects of the AT-1 receptor antagonist irbesartan on B-type natriuretic peptide (BNP), a plasmatic marker increased in patients with myocardial ischemia, on Toll-like receptors (TLRs) pathway and on oxidative balance
Previous studies have demonstrated that AT1 blockers reduced ischemic factors and the consequences of excessive reactive oxygen species (ROS) production; these effects were investigated in experimental models of atherosclerosis and in clinical trials [31,32]
Summary
Myocardial infarction (MI) is one of major cause of death and disability worldwide [1]. Clinical data have demonstrated in patients with high-risk of hypertension that irbesartan reduced inflammation, oxidative stress and exerted beneficial effects on metabolic syndrome [14].The inflammatory response plays an important role in patients with cardiovascular disease and may be useful in the diagnosis of apparently healthy subjects without known coronary artery disease and without conventional risk factors. In the present study we evaluated the antiinflammatory and antioxidant activity of irbesartan in a murine cellular model, HL-1 cardiomyocytes, exposed to hypoxic stress. For this purpose we investigated the beneficial effects of the AT-1 receptor antagonist irbesartan on B-type natriuretic peptide (BNP), a plasmatic marker increased in patients with myocardial ischemia, on TLRs pathway and on oxidative balance
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