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.

[1]  K. Hirata,et al.  Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study , 2003, Thorax.

[2]  K. Hirata,et al.  Association between the angiotensin-converting enzyme gene polymorphisms and tissue oxygenation during exercise in patients with COPD. , 2002, Chest.

[3]  K. Hirata,et al.  Deletion polymorphisms in the angiotensin converting enzyme gene are associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease. , 2000, American journal of respiratory and critical care medicine.

[4]  J. Connell,et al.  Mistyping of the human angiotensin-converting enzyme gene polymorphism: frequency, causes and possible methods to avoid errors in typing. , 1996, Journal of molecular endocrinology.

[5]  S. Rich,et al.  The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. , 1992, The New England journal of medicine.

[6]  F. Soubrier,et al.  PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). , 1992, Nucleic acids research.

[7]  S. Rich,et al.  High dose titration of calcium channel blocking agents for primary pulmonary hypertension: guidelines for short-term drug testing. , 1991, Journal of the American College of Cardiology.

[8]  R. Rogers,et al.  Oxygen consumption of the respiratory muscles in normal and in malnourished patients with chronic obstructive pulmonary disease. , 1989, The American review of respiratory disease.

[9]  B. Brundage,et al.  High-dose calcium channel-blocking therapy for primary pulmonary hypertension: evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy. , 1987, Circulation.

[10]  A. Esteban,et al.  Hemodynamic effects of vasodilators on pulmonary hypertension in decompensated chronic obstructive pulmonary disease , 1985, Critical care medicine.

[11]  M. Packer Therapeutic application of calcium-channel antagonists for pulmonary hypertension. , 1985, The American journal of cardiology.

[12]  B. Burrows Arterial oxygenation and pulmonary hemodynamics in patients with chronic airways obstruction. , 1974, The American review of respiratory disease.

[13]  R. Kacmarek,et al.  Comparison of the effects of nitric oxide, nitroprusside, and nifedipine on hemodynamics and right ventricular contractility in patients with chronic pulmonary hypertension. , 2001, Chest.

[14]  Phillips Yy,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. , 1987, The American review of respiratory disease.