Angiotensin II Receptor Antagonists in the Treatment of Hypertension


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Abstract

The orally acting nonpeptidic angiotensin II receptor blockers currently are being developed for hypertension, congestive heart failure, and renal protection. These druge potentially offer two broad cardiovascular effects. First, they antagonize the vasoconstrictor actions of angiotensin II, thereby reducing blood pressure in hypertension and decreasing afterload in heart failure. Second, by blocking the growth-promoting actions of angiotensin II, they might limit vascular hypertrophy and atherosclerosis, regress left ventricular hypertrophy, an reduce intraglomerular pressure. These druge differ mechanistically from the angiotensin-converting enzyme (ACE) inhibitors. The ACE inhibitors may not fully block angiotensin II formation, particularly as chymase and other enzymes might allow the ACE enzyme to be by-passed and depend on bradykinin accumulation for at least part of their action. This, perhaps, explains the cough seen in patients taking ACE inhibitors. The angiotensin antagonists work seletively at the AT1 receptor, but have no effect at the AT2 recepfor. Recent discoveries suggest that this selectivity might amplify the growth-inhibitory actions of these drugs. Studies with ambulatory blood pressure monitoring have shown that the angiotensin antagonists produce smooth antihypertensive actions throughout the day. Their efficacy appears similar to that of other widely used drug classes. Their hemodynamic actions in heart failure are similar to those of ACE inhibitors but clinical events and survival data are not yet available for this indication. Likewise, these drugs resemble the ACE inhibitors in their beneficial actions on renal hemodynamics and proteinuria. Pretiminary studies indicate that the angiotensin antagonists are metabolically neutral. Major clinical trials with morbidity and mortality endpoints have been initiated. It is expected that the results will be available relatively early in the history of these agents

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