Abstract
Inhibition of pulmonary capillary endothelium-bound (PCEB) ACE has been suggested as the locus of the antihypertensive action of ACE inhibitors. The purpose of this study was to contrast the enalaprilat-induced inhibition of PCEB and serum (SE) ACE activities. For PCEB ACE measurements, the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (40µCi or 2 nmol), was injected as a bolus into a central vein and immediately blood was withdrawn from a radial artery catheter. Plasma concentrations of surviving substrate (S) and product (P: 3H-benzoyl-Phe) were estimated and enzyme activity, v=1n[(S+P)/S], was calculated over the entire arterial outflow concentration curve. In chronically treated patients (n=6; 10 mg/day enalapril, p. o.) both PCEB and SE ACE were significantly reduced compared to a group (n=7) of untreated patients (0.54±0.1 vs 1.35±1=0.17 and 1.3±0.1 U/ml vs. 2.75±0.2 U/ml). In a second, acute study, similar parameters were estimated at baseline (T1) and at 15 min (T2) and 2 h (T3) after iv. administration of 1.5 µg/kg enalaprilat (n=6; patients undergoing diagnostic video assisted thoracic surgery). This treatment had no significant effect on mean arterial pressure (91±3 vs. 86±3 mmHg for T1, T2 and T3, respectively), but significantly decreased PCEB and SE ACE activities. When normalized to pre-drug (T1) activity levels, enalaprilat inhibited PCEB and ACE activity at T2 by 74±3% and 67±2%, respectively. Two hours after enalaprilat, however (T3), PCEB ACE inhibition was 66±2%, whereas SE ACE inhibition was reduced to 32±3%, suggesting tissue specificity for the inhibitory actions of enalaprilat. This procedure can be used to a) estimate changes in PCEB ACE activity in the lung, b) distinguish between SE and tissue effects of ACE inhibitors, and c) aid in the development of tissue-specific ACE inhibitors.
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© 1996 Plenum Press, New York
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Cziraki, A., Rubin, J.W., Finney, N.R., Catravas, J.D. (1996). Quantification of Pulmonary Capillary Surface Area in Patients Undergoing Coronary Arterial Bypass Grafting. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0355-8_30
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DOI: https://doi.org/10.1007/978-1-4613-0355-8_30
Publisher Name: Springer, Boston, MA
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