Key result
Enalapril 5 mg daily for 1 week significantly reduced pulmonary ACE binding by 84% in normal subjects (p<0.05) and 76% in patients with primary pulmonary hypertension (p<0.01).
Why the study?
Does enalapril 5 mg daily reduce pulmonary ACE binding in normal subjects and patients with primary pulmonary hypertension?
Does enalapril 5 mg daily reduce pulmonary ACE binding in normal subjects and patients with primary pulmonary hypertension?
Effect estimate: 76% decrease
p-value: p=<0.01
Low doses of ACE inhibitors significantly reduce pulmonary ACE binding in patients with primary pulmonary hypertension, suggesting potential for vascular remodeling effects.
Enalapril was associated with reduced pulmonary ACE binding in primary pulmonary hypertension; hypothesis-generating for remodeling effects, needs prospective confirmation.
Angiotensin-converting enzyme (ACE) inhibition attenuates pulmonary hypertension and delays the development of pulmonary vascular remodeling in animal models. Thus, ACE inhibition might be a useful treatment for primary pulmonary hypertension (PPH). To determine the dose of ACE inhibitor required to specifically block pulmonary ACE in humans, we measured the combined forward rate constant (CFRC) for [(18)F]-fluorocaptopril, which is proportional to the mass of ACE in the lung, using positron emission tomography (PET). In five normal subjects, CFRC was measured twice, 1 wk apart, to assess measurement reproducibility. The CFRC was 0.151 +/- 0.067 for the first measurement and 0.140 +/- 0.060 for the second measurement (p = not significant [NS]). In five normals, CFRC decreased on average 84%, from 0.177 +/- 0.053/s to 0.028 +/- 0.017/s (p < 0.05), after 1 wk ingestion of 5 mg enalapril orally once a day (the scans were performed 24 h after the last medication). Similarly, in five patients with PPH, CFRC decreased on average 76%, from 0.052 +/- 0. 020/s to 0.012 +/- 0.003 (p < 0.01), after 1 wk enalapril, despite much lower baseline values. We conclude that the total mass of pulmonary ACE appears to be significantly reduced in PPH and that only low doses of ACE inhibitors may be needed to block the effects of ACE on vascular remodeling in PPH.
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Qing et al. (2000) studied Primary pulmonary hypertension. Enalapril vs. Baseline was evaluated on Combined forward rate constant (CFRC) for [(18)F]-fluorocaptopril (76% decrease, p=<0.01). Enalapril 5 mg daily for 1 week significantly reduced pulmonary ACE binding by 84% in normal subjects (p<0.05) and 76% in patients with primary pulmonary hypertension (p<0.01).
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