Abstract
Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage, at baseline (T0) and at 15 min (T15) and 2 h (T120) after intravenous administration of 1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no significant effect on mean arterial pressure (91 ± 6 vs. 84 ± 7 vs. 88 ± 6 mm Hg for T0, T15 and T120, respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T0) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T15 74 ± 6% and 68 ± 6%, respectively. However, 2 h after enalaprilat (T120), PCEB ACE inhibition was maintained at 66 ± 7%, whereas serum ACE inhibition was reduced to 46 ± 8% (P <.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.
| Original language | English |
|---|---|
| Pages (from-to) | 213-218 |
| Number of pages | 6 |
| Journal | General Pharmacology |
| Volume | 35 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2000 |
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Keywords
- ACE
- ACE inhibitors
- Enalaprilat
- Indicator dilution
- Pulmonary endothelium
ASJC Scopus subject areas
- Pharmacology
Cite this
Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man. / Cziraki, Attila; Horváth, I.; Rubin, Joseph W.; Theodorakis, Michael; Catravas, John D.
In: General Pharmacology, Vol. 35, No. 4, 2000, p. 213-218.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantification of pulmonary capillary endothelium-bound angiotensin converting enzyme inhibition in man
AU - Cziraki, Attila
AU - Horváth, I.
AU - Rubin, Joseph W.
AU - Theodorakis, Michael
AU - Catravas, John D.
PY - 2000
Y1 - 2000
N2 - Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage, at baseline (T0) and at 15 min (T15) and 2 h (T120) after intravenous administration of 1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no significant effect on mean arterial pressure (91 ± 6 vs. 84 ± 7 vs. 88 ± 6 mm Hg for T0, T15 and T120, respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T0) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T15 74 ± 6% and 68 ± 6%, respectively. However, 2 h after enalaprilat (T120), PCEB ACE inhibition was maintained at 66 ± 7%, whereas serum ACE inhibition was reduced to 46 ± 8% (P <.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.
AB - Angiotensin converting enzyme (ACE, kininase II) is an endothelial luminal ectoenzyme expressed abundantly on the pulmonary capillary endothelium and recognized as the site for the conversion of circulating angiotensin I to II. In the present study, we have applied recently developed methodologies for assaying pulmonary capillary endothelium-bound (PCEB) ACE activity in man, to estimate the interaction of an ACE inhibitor (enalaprilat) with PCEB ACE in human subjects. Trace amounts of the specific ACE substrate, 3H-benzoyl-Phe-Ala-Pro (3H-BPAP; 40 Ci or 2 nmol), was injected as a bolus into the subclavian vein and immediately blood was withdrawn from a radial arterial catheter. Plasma concentrations of surviving substrate and product (3H-benzoyl-Phe) were estimated and BPAP utilization was calculated during a single transpulmonary passage, at baseline (T0) and at 15 min (T15) and 2 h (T120) after intravenous administration of 1.5 g/kg enalaprilat in 12 normotensive subjects. This treatment had no significant effect on mean arterial pressure (91 ± 6 vs. 84 ± 7 vs. 88 ± 6 mm Hg for T0, T15 and T120, respectively), but significantly decreased serum and PCEB ACE activities. When normalized to predrug (T0) activity levels, enalaprilat inhibited PCEB and serum ACE activities at T15 74 ± 6% and 68 ± 6%, respectively. However, 2 h after enalaprilat (T120), PCEB ACE inhibition was maintained at 66 ± 7%, whereas serum ACE inhibition was reduced to 46 ± 8% (P <.01 from PCEB ACE), suggesting a preferential PCEB ACE inhibitory effect of enalaprilat.
KW - ACE
KW - ACE inhibitors
KW - Enalaprilat
KW - Indicator dilution
KW - Pulmonary endothelium
UR - http://www.scopus.com/inward/record.url?scp=0034580597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034580597&partnerID=8YFLogxK
U2 - 10.1016/S0306-3623(01)00110-0
DO - 10.1016/S0306-3623(01)00110-0
M3 - Article
VL - 35
SP - 213
EP - 218
JO - Vascular Pharmacology
JF - Vascular Pharmacology
SN - 1537-1891
IS - 4
ER -