Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure
Pharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac remodeling, apoptosis, and left ventricular (LV) function after experimental myocardial infarction (MI). C57J/bl6 mice were subjected to coronary artery ligation and were treated for 10 days with vehicle or aliskiren (50 mg/kg per day via an SC osmopump), whereas sham-operated animals served as controls. This dose of aliskiren, which did not affect systemic blood pressure, improved systolic and diastolic LV function, as measured by the assessment of pressure-volume loops after MI. Furthermore, after MI LV dilatation, cardiac hypertrophy and lung weights were decreased in mice treated with aliskiren compared with placebo-treated mice after MI. This was associated with a normalization of the mitogen-activated protein kinase P38 and extracellular signal-regulated kinases 1/2, AKT, and the apoptotic markers bax and bcl-2 (all measured by Western blots), as well as the number of TUNEL-positive cells in histology. LV dilatation, as well as the associated upregulation of gene expression (mRNA abundance) and activity (by zymography) of the cardiac metalloproteinase 9 in the placebo group after MI, was also attenuated in the aliskiren-treated group. Aliskiren improved LV dysfunction after MI in a dose that did not affect blood pressure. This was associated with the amelioration of cardiac remodelling, hypertrophy, and apoptosis.
|Keywords||Aliskiren, Cardiac remodeling, Matrix metalloproteinase, Myocardial infarction, Renin inhibitor|
|Persistent URL||dx.doi.org/10.1161/HYPERTENSIONAHA.108.116350, hdl.handle.net/1765/29273|
|Note||Free full text at PubMed|
Westermann, D., Riad, A., Lettau, O., Roks, A.J.M., Sawatis, K., Becher, P.M., … Tschöpe, C.. (2008). Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure. Hypertension, 52(6), 1068–1075. doi:10.1161/HYPERTENSIONAHA.108.116350