Abstract
We investigated the role of the interaction between hypertension and the renin-angiotensin system in the pathophysiology of myocardial ischemia/reperfusion injury. We hypothesized that in the early phase of angiotensin II (ANG II)-dependent hypertension with developed left ventricular hypertrophy, cardioprotective mechanism(s) are fully activated. The experiments were performed in transgenic rats with inducible hypertension, noninduced rats served as controls. The early phase of ANG II-dependent hypertension was induced by five-days (5 days) dietary indole-3-carbinol administration. Cardiac hypertrophy, ANG II and ANG 1–7 levels, protein expression of their receptors and enzymes were determined. Separate groups were subjected to acute myocardial ischemia/reperfusion injury, and infarct size and ventricular arrhythmias were assessed. Induced rats developed marked cardiac hypertrophy accompanied by elevated ANG levels. Ischemia/reperfusion mortality was significantly higher in induced than noninduced rats (52.1 and 25%, respectively). The blockade of AT1 receptors with losartan significantly increased survival rate in both groups. Myocardial infarct size was significantly reduced after 5 days induction (by 11%), without changes after losartan treatment. In conclusion, we confirmed improved cardiac tolerance to ischemia/reperfusion injury in hypertensive cardiohypertrophied rats and found that activation of AT1 receptors by locally produced ANG II in the heart was not the mechanism underlying infarct size reduction.
Highlights
Despite the progress in understanding the mechanisms and treatment options for cardiovascular diseases (CVDs), ischemic heart disease (IHD) is among the major causes of morbidity and mortality worldwide
We investigated the role of the interaction between hypertension and the renin-angiotensin system in the pathophysiology of myocardial ischemia/reperfusion injury
The cardiac hypertrophy was accompanied by elevated heart ANG angiotensin II (II) level (19.7 ± 0.4 vs. 14.4 ± 1.4 fmol/g) that was lowered by losartan treatment as observed in NI rats (Figure 1B)
Summary
Despite the progress in understanding the mechanisms and treatment options for cardiovascular diseases (CVDs), ischemic heart disease (IHD) is among the major causes of morbidity and mortality worldwide. Reperfusion of ischemic myocardium is the most effective strategy to reduce infarct size and improve the clinical outcome. This therapy has become a “golden standard” in the treatment since the 1970s (Ginks et al, 1972; Maroko et al, 1972). The exact mechanisms of I/R injury are not fully understood but it may paradoxically diminish the beneficial effects of myocardial reperfusion. Reperfusion itself leads per se to accelerated and additional myocardial injury beyond that generated by the primary ischemia alone (Bulluck et al, 2016)
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