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Beta 1 adrenoceptor blockade promotes angiogenesis in hypertrophied myocardium of transverse aortic constricted mice
Author(s) -
Kakaraparthi Ajith,
Potnuri Ajay,
Allakonda Lingesh
Publication year - 2021
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13389
Subject(s) - medicine , cardiology , angiogenesis , muscle hypertrophy , vascular remodelling in the embryo , fibrosis , cardiac function curve , myocardial fibrosis , heart failure , endocrinology
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.