Acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in patients with chronic obstructive pulmonary disease: implication of the angiotensin-converting enzyme gene polymorphisms.
The angiotensin-converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance in tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). This study was designed to examine the acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in COPD patients with II, ID, and DD genotypes. Thirty-three COPD patients (II = 12, ID = 11, DD = 10) with placebo or nifedipine (10 mg) underwent right heart catheterization with exercise, and systemic and pulmonary haemodynamic variables were examined. At rest, there was no significant difference in either mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) or oxygen delivery (DO2) among the three groups. However, the magnitude of mPAP or PVR after exercise was the DD > ID > II genotype. In contrast, the magnitude of DO2 after exercise was the II > ID > DD genotype. We also found that nifedipine administration significantly decreased mPAP after exercise in all the three groups. However, we found no significant difference in PVR or DO2 between placebo and nifedipine administration in all the three groups. Thus, a single administration of nifedipine may not have the clinical efficacy for the treatment of pulmonary hypertension and impaired oxygen delivery during exercise in COPD patients with different ACE gene polymorphisms.
Kanazawa
Hiroshi
H
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-5-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan. kanazawa-h@med.osaka-cu.ac.jp
Tateishi
Yoshitaka
Y
Yoshikawa
Junichi
J
D000368:Aged; D001692:Biological Transport / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D005838:Genotype; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D010100:Oxygen / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy / Q000235:genetics*
D002121:Calcium Channel Blockers; D007703:Peptidyl-Dipeptidase A; D009543:Nifedipine; D010100:Oxygen