Anti-ischaemic effects of converting enzyme inhibitors: underlying mechanisms and future prospects.

ACE inhibitors have the potential to affect myocardial ischaemia in patients with asymptomatic ventricular dysfunction and ischaemic cardiomyopathy after long-term treatment. However, anti-ischaemic effects are virtually absent in stable effort angina during short-term therapy, which suggests different mechanisms of action in different patient subtypes. Long-term treatment in left ventricular dysfunction may lead to a reduction in myocardial oxygen demand and ischaemia as a result of ventricular remodelling, possibly supported by structural coronary vascular effects, i.e., an improved endothelial function and vasodilator capacity. An alternative mechanism by which ACE inhibitors may affect ischaemia, is through modulation of ischaemia-induced neurohormonal activation and subsequent systemic vasoconstriction. Depending on the severity of ischaemia, pronounced catecholamine activation and stimulation of the circulating renin-angiotensin system occur, accompanied by systemic vasoconstriction and an increase in afterload. These changes are marked in patients with left ventricular dysfunction. Moreover, a change from net catecholamine release to uptake in the ischaemic area is observed. Although the clinical significance of the latter observation is still unclear, sympathetic activation may lead to coronary vasoconstriction in stenotic areas where normal endothelium-dependent coronary vasodilatation has become impaired. In the resting patient, enalaprilat and perindoprilat significantly reduce myocardial ischaemia, not by a direct effect on the oxygen supply-demand ratio, but through modulation of neurohormonal activation, in particular of sympathetic activation during ischaemia, and, subsequently, by preventing systemic vasoconstriction. These effects are pronounced in left ventricular dysfunction, at least where perindoprilat is concerned. The possibility that ACE inhibitors improve endothelial function in concert with their modulating effects on ischaemia-induced neurohormonal activation and hence influence the occurrence of myocardial ischemia during long-term treatment needs further evaluation.