JOURNAL ARTICLE
REVIEW

[Renin-angiotensin system and its role in cardiovascular physiopathology and therapy]

Paulo Castro-Chaves, Adelino F Leite-Moreira
Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology 2004, 23: II61-77
15222251
Angiotensin II (Ang II) is an octapeptide with a central role in cardiovascular homeostasis and actions in several organs including the adrenal gland, kidney, brain, heart, smooth muscle cells and sympathetic nervous system. At these levels it is involved in cellular proliferation and apoptosis, cellular migration, inflammation, synthesis and release of various mediators such as platelet-derived growth factor and endothelin-1) and in the synthesis of extracellular matrix. Traditionally, Ang II was considered a systemic hormone regulating blood pressure, aldosterone release and sodium reabsorption. However, nowadays it is known that this mediator is also formed at the tissue level in the brain, kidney and heart, suggesting local paracrine and autocrine action. At the vascular level, with the exception of renin, all other components of this system are locally produced in vascular adventitia, smooth muscle cells or endothelial cells. In the heart all the components have also been found and their response to humoral, nervous and mechanical stimuli suggests a working local system. Ang II exerts its biological action through two main receptor subtypes: AT-1 and AT-2. The AT-1 receptor is responsible for many of the physiological effects of Ang II in cardiac, vascular, kidney, brain and endocrine cells. Expression of the AT-2 receptor is higher in fetal tissue, especially in mesenchymal tissue (like the tongue, endoderm and diaphragm), decreasing after birth. Its effects are frequently opposite to those mediated bt the AT-1 receptor. Its role in cardiovascular pathophysiology is not yet established. Ang II recruits a complex cascade of intracellular second messengers with different patterns of temporal activation: immediate (in seconds), early (in minutes) and late (in hours). Clinical trials using angiotensin converting enzyme inhibitors (ACEi) and AT-1 receptor antagonists (ARA) have shown improvement in morbidity and mortality in hypertension, congestive heart failure and after myocardial infarction. Although many of the mechanisms underlying these actions are not fully understood, there are no doubts about the beneficial effects of inhibiting this system in the treatment of several cardiovascular diseases.

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