Myocardial angiotensin receptors in human hearts

Abstract

The cardiac renin angiotensin system (RAS) is the target for number of therapeutic interventions which proved successful in heart failure. Angiotensin converting enzyme (ACE) inhibitors belong to the most efficient strategies available and angiotensin receptor (ATR) antagonists may be comparably effective. The direct myocardial effects of both classes of substances depend on the cardiac ANG II receptors. Both subtypes, AT₁ and AT₂, are expressed in the human heart. AT₁ is localized on myocytes, non-myocytes, vascular smooth muscle and endothelial cells, nerve endings, and conduction tissues. AT₂ has so far been found in fibrous tissue and endothelial cells. AT₁ mediates myocyte hypertrophy, fibroblast proliferation, collagen synthesis, smooth muscle cell growth, endothelial adhesion molecule expression, and catecholamine synthesis. AT₁ is downregulated in cardiac failure as well as in the hypertrophied transplanted heart, indicating that a 50% loss of AT₁ does not impede cardiac hypertrophy.

In heart failure therapy, AT₁ antagonists differ from ACE inhibitors by their inhibition of the degradation of bradykinin. Bradykinin has a number intrinsic effect including vasodilation, proinflammatory actions, and modulation of fibrous tissue synthesis. In addition to bradykinin, the functional role of AT₂ seems crucial for the therapeutic differences of AT₁ antagonists versus ACE inhibitors.