Aliskiren, a member in the family of RAAS-blockers, is a direct renin inhibitor indicated for the treatment of hypertension. Aliskiren is the first orally effective direct renin inhibitor to be used clinically, and it may offer benefits in cardiovascular disease over and above those achieved with conventional renin‐angiotensin system (RAS) blocking strategies. Furthermore, the beneficial effects of aliskiren on cardiac function were independent of blood pressure.
This study was designed to explore the beneficial effect of aliskiren on myocardial infarction (MI) in a model of surgically induced myocardial infarction in rats and its potential effect on heart failure (HF) in a model of isoprenaline induced heart failure in rats. This study was designed to study two models, model of MI and model of HF.
As regard the model of MI, rats were used and divided into four equal groups: normal control group, MI with no medication group, MI L-NAME group (received L-NAME 20 mg/kg for 4 weeks as a method for induction of hypertension) and aliskiren treated MI L-NAME group (received L-NAME 20mg/kg and aliskiren 50 mg/kg for 4 weeks).
The blood pressure was measured after the end of the 4 th week just before induction of MI. MI was experimentally induced by ligation of left anterior descending (LAD) coronary artery for 30 minutes then the ligature was cut to allow cardiac reperfusion for 2 hours. After the 2 hours of reperfusion, rats were subjected to measure cardiac enzymes (troponin and CPK-MB) and ECG changes (T-wave and heart rate) and scarified to measure infarction size.
It was found that treatment of rats with aliskiren 50 mg/kg IP for 4 weeks produce significant reduction of systolic and diastolic blood pressure when compared to MI L-NAME group. In comparison to MI with no medication and MI L-NAME group, it produced significant reduction of cardiac enzymes (troponin and CPK-MB), heart rate and T–wave voltage, also the infarction size was significantly reduced in rats treated with aliskiren.
As regard the model of HF, rats were used and divided into three equal groups: normal control group, HF group with no medication and aliskiren treated HF group (received aliskiren 50 mg/kg for 2 weeks).
HF was experimentally induced by subcutaneous injection of isoprenaline (150mg/kg) dissolved in saline. Surviving animals were used for the experiment for 2 weeks.
By the end of the study period, 2 weeks, all rats were subjected to measure systolic and diastolic blood pressure, heart rate and ejection fraction and scarified to study histopathological changes of the heart.
Data obtained from the present study pointed out that daily administration of aliskiren 50 mg/kg IP for 2 weeks produced significant reduction of systolic and diastolic blood pressure when compared to normal control group. In comparison to HF group, it produced insignificant change of systolic and diastolic blood pressure, significant reduction of heart rate and significant improvement of ejection fraction.
Histopathological examination of cardiac sections of control group showed no detectable abnormality in cardiac smooth muscle cells. Sections of heart failure group revealed myocyte degeneration and necrosis and interstitial fibrosis. Aliskiren administration significantly decreases these changes.
In conclusion, it was found that treatment with aliskiren which inhibit the primary rate limiting step in RAS (renin inhibition), was effective in controlling systemic blood pressure which was proved by reduction of blood pressure in rats treated with aliskiren when compared to those receiving L-NAME. Also, aliskiren had protective effect against MI which was proved by lowering the leakage of the cardiac biomarkers (CPK-MB and troponin level) & reduction of ECG changes as heart rate as well as T-wave voltage with reduction of infarction size in aliskiren treated group in comparison to MI with no medication and MI L-NAME group. Aliskiren also improved heart failure which was proved by reduction of heart rate and increase of ejection fraction with improvement of histopathological picture of heart in aliskiren treated group when compared to heart failure group.