Beta 1 adrenoceptor blockade promotes angiogenesis in hypertrophied myocardium of transverse aortic constricted mice

Left ventricular hypertrophy (LVH) is an adaptive structural remodelling consequent to uncontrolled blood pressure. Impaired angiogenesis plays a vital role in transiting LVH into cardiac failure. Catecholamines modulate myocardial function through beta adrenoceptors, and their blockers (β-AR) reduce cardiovascular morbidity and mortality by decelerating the LVH progression. Nonetheless, the effect of β-AR blockers on myocardial vascular bed remains largely obscure. Hence, this study is focussed on analysing the possible outcomes of β-AR blockers on myocardial vascular remodelling using a surgically induced LVH mice model. Transverse aortic constricted mice and sham-operated mice were administered with metoprolol at a dose of 30 mg/kg/d for 60 days and myocardial vascular endothelial growth factor (VEGF) alpha levels, GSH/GSSG ratio, myocardial protein carbonyl content, hypertrophy index and global myocardial function, trans-aortic fluid dynamics and expression pattern of angiopoietin-1 and VEGF alpha were assessed. These findings were further confirmed by histochemical analysis for myocardial capillary density, perivascular fibrosis ratio and intimal thickening. Sub- chronic β-AR blockade reduced the oxidative stress, hypertrophic index, intimal thickening and perivascular fibrosis ratio. A marked increase in myocardial VEGF, angiopoietin 1, global myocardial function and myocardial capillary density was also observed. There was a reduction in the LVH and upregulation of myocardial angiogenesis concluding that β-AR blockers prevent adverse vascular remodelling which might underlie its concealed mechanism of action.