title: Angiotensin II type 1 receptor antagonists in animal models of vascular, cardiac, metabolic and renal disease.
abstract: We have reviewed the effects of angiotensin II type 1 receptor antagonists (ARBs) in various animal models of hypertension, atherosclerosis, cardiac function, hypertrophy and fibrosis, glucose and lipid metabolism, and renal function and morphology. Those of azilsartan and telmisartan have been included comprehensively whereas those of other ARBs have been included systematically but without intention of completeness. ARBs as a class lower blood pressure in established hypertension and prevent hypertension development in all applicable animal models except those with a markedly suppressed renin-angiotensin system; blood pressure lowering even persists for a considerable time after discontinuation of treatment. This translates into a reduced mortality, particularly in models exhibiting marked hypertension. The retrieved data on vascular, cardiac and renal function and morphology as well as on glucose and lipid metabolism are discussed to address three main questions: 1. Can ARB effects on blood vessels, heart, kidney and metabolic function be explained by blood pressure lowering alone or are they additionally directly related to blockade of the renin-angiotensin system? 2. Are they shared by other inhibitors of the renin-angiotensin system, e.g. angiotensin converting enzyme inhibitors? 3. Are some effects specific for one or more compounds within the ARB class? Taken together these data profile ARBs as a drug class with unique properties that have beneficial effects far beyond those on blood pressure reduction and, in some cases distinct from those of angiotensin converting enzyme inhibitors. The clinical relevance of angiotensin receptor-independent effects of some ARBs remains to be determined.
authors.affiliation: Dept. Pharmacology, Johannes Gutenberg University, Mainz, Germany; Dept. Translational Medicine & Clinical Pharmacology, Boehringer Ingelheim, Ingelheim, Germany. Electronic address: marmiche@uni-mainz.de.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.affiliation: Emeritus of Lausanne University, Riehen, Switzerland.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Brunner
authors.affiliation: Retiree from Dept. of Research Networking, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Foster
authors.affiliation: Dept. Cardiology & Heart Center, Peking University First Hospital, Beijing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D046508:Culture Techniques; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D010069:Oxadiazoles / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects; D020521:Stroke / Q000517:prevention & control; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D010069:Oxadiazoles; C521273:azilsartan; D005947:Glucose; D000077333:Telmisartan