The renin-angiotensin system in heart failure

The renin-angiotensin aldosterone system does appear to have a central role in the haemodynamic and metabolic response to declining ventricular function. Human heart failure usually occurs in the setting of preceding disease, which may itself influence the underlying activity of the system. Studies of the renin-angiotensin system after myocardial infarction are in agreement with animal models, that transient activation of the renin-angiotensin system occurs. This may be sustained if the cardiac insult is severe and especially if diuretic therapy is initiated. In those patients in whom the insult is less severe, activity of the renin-angiotensin system wanes. The finding that patients with stable untreated heart failure do not have markedly activated renin-angiotensin systems is not surprising, but correction of the plasma and extracellular volume (for instance with a diuretic) will result in reappearance of activation of these systems. Since the introduction of angiotensin-converting enzyme inhibitors, several new peptides have been discovered (atrial natriuretic peptide, endothelin etc.) that have important effects on cardiovascular function. New potential therapeutic agents with actions on neuroendocrine systems, such as the atrial peptidase inhibitors, angiotensin-II receptor antagonists and renin inhibitors, are on the horizon. Such exciting new discoveries will give as much insight into the pathophysiology of heart failure as the angiotensin-converting enzyme inhibitors have done.