Role of peptidases in bradykinin-induced increase in vascular permeability in vivo

T. Yong, Pei Gao Xiao Pei Gao, S. Koizumi, J. M. Conlon, S. I. Rennard, W. G. Mayhan, I. Rubinstein

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The purpose of this study was to examine whether neutral endopeptidase and angiotensin I-converting enzyme, two membrane-bound metalloenzymes that are widely distributed in the microcirculation, play a role in bradykinin-induced increase in vascular permeability in the hamster cheek pouch. Changes in vascular permeability were quantified by counting the number of leaky sites and by calculating the clearance of fluorescein isothiocyanate (FITC)-dextran (molecular mass, 70,000 d) during suffusion of the cheek pouch with bradykinin. Bradykinin produced a concentration- and time-dependent increase in the number of leaky sites and clearance of FITC-dextran. The selective, active site-directed neutral endopeptidase inhibitors phosphoramidon (1.0 μM) and thiorphan (10.0 μM) and the selective angiotensin I-converting enzyme inhibitor captopril (10.0 μM) each shifted the concentration-response curve to bradykinin significantly to the left. During suffusion with bradykinin (1.0 μM) and phosphoramidon, the number of leaky sites increased significantly from 17±2 to 27±4 sites per 0.11 cm2 (mean±SEM, p<0.05), and FITC-dextran clearance increased significantly from 1.0±0.2 to 2.1±0.3 ml/secx10-6. During suffusion with bradykinin (1.0 μM) and captopril, the number of leaky sites increased significantly from 10±2 to 41±3 sites per 0.11 cm2, and FITC-dextran clearance increased significantly from 0.8±0.3 to 3.2±0.8 ml/secx10-6. During suffusion with bradykinin (1.0 μM) and thiorphan, the number of leaky sites increased significantly from 15±3 to 47±7 sites per 0.11 cm2, and FITC-dextran clearance increased significantly from 0.8±0.2 to 4.7±0.6 ml/secx10-6. Suffusion of both phosphoramidon and captopril was associated with an additive effect on bradykinin-induced responses. Other proteinase inhibitors had no significant effect on bradykinin-induced increase in vascular permeability. In addition, adenosine (1.0 μM)-induced increase in leaky site formation was not potentiated by phosphoramidon and captopril. We conclude that neutral endopeptidase and angiotensin I-converting enzyme each play an important role in modulating bradykinin-induced increase in vascular permeability in vivo.

Original languageEnglish (US)
Pages (from-to)952-959
Number of pages8
JournalCirculation Research
Volume70
Issue number5
StatePublished - Jan 1 1992

Fingerprint

Capillary Permeability
Bradykinin
Peptide Hydrolases
Captopril
Neprilysin
Thiorphan
Cheek
Peptidyl-Dipeptidase A
Microcirculation
Protease Inhibitors
Angiotensin-Converting Enzyme Inhibitors
Cricetinae
Adenosine
Catalytic Domain
fluorescein isothiocyanate dextran
Membranes
phosphoramidon

Keywords

  • angiotensin I-converting enzyme
  • hamsters
  • inflammation
  • microcirculation
  • neutral endopeptidase
  • proteinase inhibitors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Yong, T., Xiao Pei Gao, P. G., Koizumi, S., Conlon, J. M., Rennard, S. I., Mayhan, W. G., & Rubinstein, I. (1992). Role of peptidases in bradykinin-induced increase in vascular permeability in vivo. Circulation Research, 70(5), 952-959.

Role of peptidases in bradykinin-induced increase in vascular permeability in vivo. / Yong, T.; Xiao Pei Gao, Pei Gao; Koizumi, S.; Conlon, J. M.; Rennard, S. I.; Mayhan, W. G.; Rubinstein, I.

In: Circulation Research, Vol. 70, No. 5, 01.01.1992, p. 952-959.

Research output: Contribution to journalArticle

Yong, T, Xiao Pei Gao, PG, Koizumi, S, Conlon, JM, Rennard, SI, Mayhan, WG & Rubinstein, I 1992, 'Role of peptidases in bradykinin-induced increase in vascular permeability in vivo', Circulation Research, vol. 70, no. 5, pp. 952-959.
Yong T, Xiao Pei Gao PG, Koizumi S, Conlon JM, Rennard SI, Mayhan WG et al. Role of peptidases in bradykinin-induced increase in vascular permeability in vivo. Circulation Research. 1992 Jan 1;70(5):952-959.
Yong, T. ; Xiao Pei Gao, Pei Gao ; Koizumi, S. ; Conlon, J. M. ; Rennard, S. I. ; Mayhan, W. G. ; Rubinstein, I. / Role of peptidases in bradykinin-induced increase in vascular permeability in vivo. In: Circulation Research. 1992 ; Vol. 70, No. 5. pp. 952-959.
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