Drugs affecting the renin-angiotensinaldosterone system and ischemic heart disease

Abstract

The renin-angiotensin-aldosterone (RAAS) system is a multilayered cascade of mediators involved in regulation of arterial pressure, tissue perfusion and extracellular volume, and hence the cardiovascular and renal homeostasis. Classicaly, the system has been seen as consisting of angiotensinogen substrate and two enzymes, renin and angiotensin-converting enzyme, which sequentially convert it to angiotensin I and II. Angiotensin II, the main effector of the cascade, acts through two subtypes of angiotensin receptors, and gives rise to rapid and slow pressor response and vascular and cardiac hypertrophy and remodeling. Additionally, it regulates release of mineralocorticoid hormone aldosterone from adrenal cortex. The expanded view of RAAS system covers a number of other angiotensins (III, IV, 1-7), as well as newlycharacterized enzymes and receptors. Five classes of drugs directly affect the activity of this cascade: antagonists of β adrenergic receptors, renin inhibitors, angiotensinconverting enzyme inhibitors, antagonists of angiotensin receptor subtype 1 and antagonists of mineralocorticoid receptors. It was shown that angiotensin-converting enzyme inhibitors, but not antagonists of angiotensin receptor, can be beneficial in primary and secondary prevention of myocardial infarction, and this class of drugs should be used as a first -line treatment in patients with ischemic heart disease requiring suppression of RAAS axis.

Sistem renin-angiotenzin-aldosteron (RAAS) predstavlja višeslojnu kaskadu medijatora uključenih u regulaciju arterijskog pritiska, perfuzije tkiva i ekstracelularnog volumena, i time homeostazu kardiovaskularnog sistema i bubrega. Klasično viđenje je da se RAAS sistem sastoji od supstrata angiotenzina i dva enzima, renina i angiotenzinkonvertujućeg enzima, koji sekvencijalno prevode supstrat u angiotenzin I i II. Angiotenzin II, glavni efektor kaskade, deluje preko dva podtipa receptora za angiotenzin i dovodi do brze i spore komponente porasta krvnog pritiska, hipertrofije i remodelovanja srca i krvnih sudova. Dodatno, angiotenzin II reguliše i oslobađanje mineralokortikoidnog hormona aldosterona iz kore nadbubrežnih žlezda. Prošireno viđenje RAAS sistema obuhvata i jedan broj drugih angiotenzina (III, IV, 1-7), kao i novo-karakterisane enzime i receptore. Pet klasa lekova direktno utiče na aktivnost ove kaskade: antagonisti β adrenergičkih receptora, inhibitori renina, inhibitori angiotenzinkonvertujućeg enzima, antagonisti receptora za angiotenzin, podtip 1, i antagonisti mineralokortikoidnih receptora. Pokazano je da inhibitori angiotenzin-konvertujućeg enzima, ali ne i antagonisti angiotenzinskih receptora, mogu da budu korisni u primarnoj i sekundarnoj prevenciji infarkta miokarda, i ovu klasu lekova treba koristiti kao terapiju prvog izbora kod pacijenata sa ishemijskom bolešću srca kod kojih je indikovana supresija RAAS osovine.