Renin-angiotensin CV physiology

From Miller “Cardiac hormones are polypeptides secreted by cardiac tissues into the circulation in the normal heart. Natriuretic peptides, aldosterone, and adrenomedullin are hormones secreted by cardiomyocytes. Angiotensin II, the effector hormone in the renin-angiotensin system, is also produced by cardiomyocytes. The renin-angiotensin system is one of the most important regulators of cardiovascular physiology. It is a key modulator of cardiac growth and function. Angiotensin II stimulates two separate receptor subtypes, AT1 and AT2, both of which are present in the heart. AT1 receptors are the predominant subtype expressed in the normal adult human heart. Stimulation of AT1 receptors induces a positive chronotropic and inotropic effect. Angiotensin II also mediates cell growth and proliferation in cardiomyocytes and fibroblasts and induces release of the growth factors aldosterone and catecholamines through stimulation of AT1 receptors. Activation of AT1 receptors is directly involved in the development of cardiac hypertrophy and heart failure, as well as adverse remodeling of the myocardium. In contrast, AT2 receptor activation is counter-regulatory and is generally antiproliferative. Expression of AT2 receptors, however, is relatively scant in the adult heart because they are most abundant in the fetal heart and decline with development. In response to injury and ischemia, AT2 receptors become upregulated. The precise role of AT2 receptors in the heart remains to be defined.

The beneficial effects of blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors in the treatment of heart failure have been attributed to inhibition of AT1 receptor activity. In addition to the renin-angiotensin system, other cardiac hormones that have been shown to play pathogenic roles in the promotion of cardiomyocyte growth and cardiac fibrosis, development of cardiac hypertrophy, and progression of congestive heart failure include aldosterone, adrenomedullin, natriuretic peptides, angiotensin, endothelin, and vasopressin.”