Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure.
In chronic heart failure, angiotensin-converting enzyme inhibitors produce an acute decrease in aldosterone levels. Long-term angiotensin-converting enzyme inhibition is, however, associated with aldosterone suppression that is weak, variable, and unsustained (ie, aldosterone escapes). The possible harmful effects of this residual aldosterone are multiple Magnesium loss caused by aldosterone and by diuretics could contribute to coronary artery spasm and arrhythmias. Aldosterone blocks norepinephrine uptake by the myocardium; extracellular catecholamines may, therefore, lead to arrhythmias and ischemia. Aldosterone has been shown to have an acute arrhythmogenic effect as well as a detrimental effect on parasympathetic and baroreflex function. Both angiotensin II and aldosterone stimulate myocardial fibrosis, which may lead to a higher incidence of malignant ventricular arrhythmias. Spironolactone therapy added to the regimen of an angiotensin-converting enzyme inhibitor and diuretic has been shown to cause natriuresis, magnesium retention, increased myocardial norepinephrine uptake, and reduced incidence of ventricular arrhythmias. It may well be that residual aldosterone mediates many harmful effects in chronic heart failure and that to optimize the benefit of blocking the renin-angiotensin-aldosterone system may require specific blockade of residual aldosterone as well as traditional angiotensin-converting enzyme inhibition.
Struthers
A D
AD
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, United Kingdom.
D000450:Aldosterone / Q000009:adverse effects / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008274:Magnesium / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D000450:Aldosterone; D008274:Magnesium