title: [Pathophysiological and clinical implications of AT(1)/AT(2) angiotensin II receptors in heart failure and coronary and renal failure].
abstract: The octapeptide angiotensin II (Ang II), the potent effector molecule of the renin-angiotensin-aldosterone system (RAAS), is involved in the control of blood pressure, cardiac and vascular function as well as sodium and water homeostasis. Because Ang II has also been implicated in the pathophysiology of cardiovascular diseases and renal failure, it has been of increasing interest to inhibit the RAAS at the level of its enzymes such as renin and angiotensin-converting enzyme (ACE) and receptors. At least two subtypes of angiotensin receptors have been identified: AT(1) and AT(2). The AT(1 )receptor mediates all of the known actions of Ang II in the cardiovascular system, such as vasoconstriction, increasing cardiac contractility and renal tubular sodium reabsorption, as well as vascular and cardiac hypertrophy. In contrast, less is known regarding the function of the AT(2) receptor. Evidence suggests that the AT(2) receptor inhibits cell proliferation and induces differentiation, apoptosis and regeneration. The AT(2) receptor has been shown to reverse AT(1) receptor-mediated hypertrophy, suggesting that these receptors exert opposing effects in the cardiovascular system. While renin and ACE inhibitors block the RAAS at the enzymatic level, AT receptor antagonists specifically inhibit the RAAS at the receptor site. AT(1 )receptor antagonists induce a dose-dependent blockade of Ang II-induced effects, resulting in a reduction in blood pressure, cardiac and vascular hypertrophy, proteinuria and glomerular sclerosis. It is postulated that AT(1) receptor antagonists may provide end-organ protection by blocking Ang II via the AT(1) receptor, yet leaving the AT(2) receptor unopposed. These substances have been shown to decrease morbidity and mortality of patients with heart failure and renal disease associated with diabetes.
authors.affiliation: Institut de Pharmacologie et Toxicologie, Université de Berlin Charite-Humboldt, Berlin, Allemagne. s.sandmann@pharmakologie.uni-kiel.de
authors.forename: Steffen
authors.initials: S
authors.lastname: Sandmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D051437:Renal Insufficiency / Q000188:drug therapy / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin