Angiotensin II type-1 receptor activation in the adult heart causes blood pressure-independent hypertrophy and cardiac dysfunction

Abstract

Low-level local AT1R activity in differentiated myocardium causes compensated cardiac hypertrophy, that is, increased myocardial mass but with the retention of normal function, whereas short-term increased stimulation induces cardiac dysfunction with dilatation, reduced ejection fraction, and increased fibrosis in the absence of change in systemic BP.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…These mice develop diastolic dysfunction without developing significant cardiac hypertrophy but show progressive renal and cardiac fibrosis. Overexpression of the constitutively active N111G mutant of AT 1 receptor in cardiac myocytes produced enhanced myocyte growth from the onset of adolescence associated with cardiac hypertrophy in the adult without progressing to pathologic remodeling or HF (Ainscough et al, 2009). However, AngIV peptide infusion induced adverse ventricular remodeling within 4 weeks characterized by increased interstitial fibrosis, dilatation of the left ventricle, and impaired cardiac function.…”

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Mediates stretch-induced hypertrophy via AT1 receptor (Sadoshima et al, 1993). Induces hypertrophy through AT1 receptor independently of blood pressure elevation (Ainscough et al, 2009). Aldosterone receptor activation boosts angiotensin II-induced expansion of extracellular matrix proteins, fibrosis, and oxidative stress (Di Zhang et al, 2008).…”

Increased myocardial fibrosis and left ventricular dysfunction in Cushing's syndrome

“…These structural abnormalities can be partially explained by the rise in blood pressure, but the most important role is attributed to glucocorticoid excess, which directly activates some of the components of the rennin-angiotensin system (25,26) and in particular enhances angiotensin-II responsiveness of the myocytes (27). More importantly, control of both the MRs and the GRs appears to be critical in the regulation and development of myocardial fibrosis (28,29).…”