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Blockade of the renin-angiotensin system.

HISTORICAL OVERVIEW
Milestones in understanding the renin-angiotensin system (RAS) until the development of angiotensin II antagonists are described briefly. Sites at which the RAS might be blocked are outlined.


PEPTIDE ANALOGUE ANTAGONISTS OF ANGIOTENSIN II RECEPTORS
Saralasin-like compounds were used in numerous experimental and clinical situations and clarified the role of the RAS. Some of these situations are described (e.g. hypertension and cardiac failure) particularly in regard to the control of arterial pressure and aldosterone secretion by the RAS. Saralasin and its analogues allowed visualization, for the first time, of complete angiotensin II/effector (especially blood pressure) dose-response curves.


ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS
The clinical usefulness of ACE inhibitors in hypertension, cardiac failure, diabetes mellitus and after acute myocardial infarction is emphasized. In particular, ACE inhibitors have actions beyond blockade of angiotensin II formation, necessitating cautious interpretation of data from their use.


RENIN INHIBITORS
Experience with renin inhibitors in documenting and confirming the role of the RAS is outlined. NON-PEPTIDE ANGIOTENSIN II RECEPTOR ANTAGONISTS: Characteristics of losartan-like compounds are discussed in brief, and the results of their limited use in clinical medicine are outlined.


CONCLUSION
Blocking agents have led to great advances in knowledge of the RAS and its physiological and pathophysiological functions. ACE inhibitors are used regularly in a number of clinical disorders and, in theory, have therapeutic potential beyond alternative antihypertensive drugs in the prevention of cardiovascular complications in essential hypertension. The place of renin inhibitors and angiotensin II receptor antagonists in clinical practice, however, remains to be determined.