Left ventricular hypertrophy and angiotensin II receptor blocking agents.
Angiotensin II plays a significant role in cell growth and proliferation in model systems and in humans. Numerous studies have shown that left ventricular hypertrophy (LVH) increases the risk of coronary heart disease, congestive heart failure, stroke or transient ischemic attack; all-cause deaths, and sudden death. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided beneficial effects on LVH regression and on cardiac remodeling in the presence of hypertension and heart failure. The new class of ARBs appears to provide cardioprotective effects that are similar to those of the ACE inhibitors. Most of the beneficial effects provided by these agents appear to be related to a more complete blockade of the angiotensin II type 1 (AT1) receptor. However, costimulation of the angiotensin II type 2 (AT2) receptor appears to increase nitric oxide and thus causes some bradykinin-like effects. Evidence for the role of angiotensin II in promoting LVH as well as abnormal regulation of the angiotensin II signal transduction pathways in model systems and in humans has been reviewed. Secondly, the mechanisms for the beneficial effects of angiotensin II receptor blockers studied in model systems and in humans, including possible involvement in the formation of reactive oxygen species by mononuclear cells, are presented. Finally, results from large-scale interventions such as the Losartan Intervention For Endpoint reduction (LIFE) study, as well as an overview of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial involving the use of ARB in high-risk patients, are presented.
Yasunari
K
K
Department of Medicine and Cardiology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan. yasunari@med.osaka-cu.ac.jp
Maeda
K
K
Nakamura
M
M
Watanabe
T
T
Yoshikawa
J
J
Hirohashi
K
K
D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000378:metabolism; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D017382:Reactive Oxygen Species; D000804:Angiotensin II