Acute effects of ACE inhibition on coronary endothelial dysfunction.
The prerequisite of atherosclerosis, endothelial dysfunction, is characterised by impaired endothelium-dependent vasodilation caused by the reduced bioavailibility of nitric oxide (NO). In order to assess the role of acute ACE inhibition in this setting, coronary arterial endothelial function was quantified following acute intracoronary administration of the angiotensin-converting enzyme (ACE) inhibitor quinapril. Twenty-one patients with non-limiting coronary artery disease were studied before and after acute intracoronary administration of 10 mg quinapril. Nine patients received pre-treatment with the angiotensin AT(1)-receptor antagonist losartan (2 x 50 mg, p.o.). Coronary cross-sectional diameter was measured via quantitative angiography and microvascular reaction was investigated by intracoronary Doppler flow measurement during intracoronary infusion of 0.1 to 10 micromol/l acetylcholine. Quinapril acutely improved endothelial dysfunction on the macro- as well as the microvascular level. Losartan did not alter macrovascular function but facilitated microvascular endothelial function. Acute quinapril application led to no further improvement of endothelial dysfunction in patients pre-treated with losartan. Acute quinapril infusion improved endothelial function in patients with coronary heart disease. Treatment with the AT(1)-receptor antagonist losartan led to a slight improvement in microvascular endothelial function, but pre-treatment with losartan blunted the vascular effect of quinapril, suggesting that the combination of ACE inhibition and AT(1)-receptor antagonism may not exert a synergistic benefical impact on the coronary vasculature.
Nickenig
G
G
Universitat des Saarlandes, Homburg, 66421, Germany. nickenig@med-in.uni-sb.de
Stäblein
A
A
Wassmann
S
S
Wyen
C
C
Müller
C
C
Böhm
M
M
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D000077583:Quinapril; D044140:Receptor, Angiotensin, Type 1; D044005:Tetrahydroisoquinolines; D013997:Time Factors; D014664:Vasodilation; D014666:Vasomotor System / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044140:Receptor, Angiotensin, Type 1; D044005:Tetrahydroisoquinolines; D019808:Losartan; D000077583:Quinapril