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Angiotensin II receptor antagonists - antihypertensive agents.
Expert Opinion on Investigational Drugs
Publication types: Journal Article
Blockade of the renin-angiotensin system (RAS) is now recognised as an effective approach for the treatment of hypertension and congestive heart failure (CHF). Today, it is possible to antagonise the effects of angiotensin II more specifically by blocking its receptors using non-peptide receptor antagonists. These compounds, which at first were used to identify the various subtypes of angiotensin II receptors, are now available clinically. Some of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as angiotensin converting enzyme (ACE) inhibitors at lowering blood pressure in hypertensive patients, and appear to have similar systemic and renal haemodynamic properties in patients with CHF and renal diseases. Large-scale clinical trials such as the LIFE, the ELITE and the RENAAL studies are now underway to investigate the long-term benefits of one of these agents in hypertension, heart failure and Type II diabetic nephropathy. The major clinical advantage of AT1 receptor antagonists is that, in contrast to ACE inhibitors, they do not induce cough. With the more widespread use of AT1 receptor antagonists, two unresolved questions remains unanswered: what is the role of AT2 receptors? Are the unblocked effects of angiotensin II on AT2 receptor sites of any clinical relevance to the safety profile or efficacy of AT1 receptor antagonists? Another interesting question is whether the combination of an ACE inhibitor with an AT1 receptor antagonist is advantageous. Studies attempting to answer these questions are underway and will certainly enable researchers to define more precisely the role and the advantages of these new specific non-peptide AT1 receptor antagonists in the treatment of hypertension and heart failure.
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