Effect of ACE inhibition on neurohormones.
Long-term controlled trials in heart failure in patients with asymptomatic left ventricular dysfunction indicate the potential of ACE inhibition to reduce ischaemic events, such as unstable angina and myocardial infarction. These effects occur after long-term medication and suggest structural rather than functional effects of ACE inhibitors. Such structural effects could include an improvement in endothelial function and less atherosclerosis of coronary and systemic arteries, as well as a reduction in cardiac size. Together, these effects may improve the myocardial oxygen supply/demand ratio. Neurohormonal activation is pivotal in heart failure and also occurs in patients with asymptomatic left ventricular dysfunction. ACE inhibitors modulate neurohormonal activation and, through that mechanism, may induce their beneficial effects in terms of cardiac remodelling and improved morbidity and mortality in heart failure patients. Neurohormonal activation also occurs during acute myocardial infarction, particularly in patients with diminished left ventricular dysfunction or heart failure. Recent studies indicate that short episodes of stress-induced myocardial ischaemia may also lead to significant increases in circulating norepinephrine, epinephrine and, in more severe ischaemia, in angiotensin II. This increase in vasoconstricting neurohormones results in significant systemic vasoconstriction and may also underlie the constriction of abnormal coronary segments observed during atrial pacing-induced stress. This ischaemia-induced neurohormonal activation is not dependent on the stress of angina, but correlates with the degree of myocardial ischaemia and also with the presence of left ventricular dysfunction. Acute ACE inhibition modulates this ischaemia-induced neurohormonal activation and the subsequent effects on systemic and coronary vascular tone. Consequently, acute ACE inhibition significantly reduces acute myocardial ischaemia. The significance of these observations is as yet unclear. However, they may be important in situations of severe myocardial ischaemia, such as unstable angina and acute myocardial infarction. Presumably, this potential of ACE inhibitors to reduce short-term stress-induced myocardial ischaemia as a result of their neurohormonal modulating and subsequent vasodilating effects gains in significance during chronic ACE inhibitor treatment, in parallel with a long-term improvement of coronary endothelial function.
Remme
W J
WJ
Sticares Foundation, Rotterdam, The Netherlands.
D000804:Angiotensin II / Q000097:blood / Q000187:drug effects*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects*; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D009203:Myocardial Infarction / Q000201:enzymology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000517:prevention & control*; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine