Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study.
BACKGROUND
We have previously shown that angiotensin converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). A pilot study was designed to examine the effects of captopril on these exercise related variables in COPD patients categorised according to ACE gene polymorphisms.


METHODS
Thirty six patients with COPD (II=13, ID=11, DD=12) received oral captopril (25 mg) or placebo in a randomised, double blind, crossover manner and underwent right heart catheterisation with exercise.


RESULTS
Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and lactate concentration after exercise with both placebo and captopril were higher in patients with the DD genotype than in those with the II or ID genotypes. In contrast, mixed venous oxygen tension (PvO(2)) was lower in patients with the DD genotype than in those with the other genotypes. Moreover, mPAP, PVR, and lactate concentration after exercise were lower in the captopril group than in the placebo group in patients with the II or ID genotype, but not in those with the DD genotype. PvO(2) after exercise was higher with captopril than with placebo in patients with the II genotype, but not in those with the other genotypes.


CONCLUSIONS
These findings suggest that pulmonary haemodynamic variables and state of tissue oxygenation during exercise are dependent on ACE genotypes, and that captopril administration effectively influences these exercise related variables. Although the sample size in this pilot study was limited, it is likely that the improvement in exercise related variables in COPD patients with the II genotype is relatively sensitive to captopril.
Kanazawa
H
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Abenoku, Osaka 545-8585, Japan. kanazawa-h@med.osaka-cu.ac.jp
Hirata
K
K
Yoshikawa
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology*; D006328:Cardiac Catheterization; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005838:Genotype; D006439:Hemodynamics; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010865:Pilot Projects; D011110:Polymorphism, Genetic / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D014655:Vascular Resistance
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D010100:Oxygen