Renin-angiotensin system blockade at the level of the angiotensin converting enzyme or the angiotensin type-1 receptor: similarities and differences

• Published in: Current topics in medicinal chemistry Vol. 4; no. 4; p. 473
• Main Authors: Stergiou, George S, Skeva, Irini I
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2004
• Subjects: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - metabolism; Drug Design; Humans; Peptidyl-Dipeptidase A - metabolism; Receptor, Angiotensin, Type 1 - metabolism; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology
• ISSN: 1568-0266
• DOI: 10.2174/1568026043451320

The development of drugs which block the renin-angiotensin system (RAS) has been proven a major advance in cardiovascular medicine. Angiotensin converting enzyme (ACE) inhibitors, which block the formation of angiotensin II from the inactive angiotensin I, are widely used as first line treatment in hypertension, heart failure and diabetic nephropathy. More recently, selective antagonists of the angiotensin type-1 receptor (AT1R) have become available for clinical use. Accumulating evidence suggests that AT1R antagonists have similar effects to ACE inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE inhibitors and AT1R antagonists block the same system, experimental evidence suggest that their mechanisms of action differ in several respects, such as increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R activation with AT1R antagonists. Nevertheless, the clinical significance of these differences remains largely unknown and, in practice, the only clear advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a side effect. Recent clinical data suggest that combined ACE inhibition and AT1R antagonism offer additive effects in reducing blood pressure in hypertension, in reducing proteinuria in nephropathy and in improving prognosis in heart failure. Further evidence suggests that some hypertensive patients may have a good antihypertensive response with ACE inhibition but not with AT1R antagonism, or the reverse. These data suggest that these two drug classes have important similarities, because they act on the same system, but they also appear to have important differences, which are not only of theoretical but also of clinical importance.