TY - JOUR
T1 - Role of peptidases in bradykinin-induced increase in vascular permeability in vivo
AU - Yong, Tan
AU - Gao, Xiao Pei
AU - Koizumi, Shin
AU - Conlon, J. Michael
AU - Rennard, Stephen I.
AU - Mayhan, William G.
AU - Rubinstein, Israel
PY - 1992/5
Y1 - 1992/5
N2 - 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/sec×10-6. 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/sec×10-6. 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/sec×10-6. 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.
AB - 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/sec×10-6. 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/sec×10-6. 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/sec×10-6. 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.
KW - Angiotensin I-converting enzyme
KW - Hamsters
KW - Inflammation
KW - Microcirculation
KW - Neutral endopeptidase
KW - Proteinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=0026515127&partnerID=8YFLogxK
M3 - Article
C2 - 1314717
AN - SCOPUS:0026515127
SN - 0009-7330
VL - 70
SP - 952
EP - 959
JO - Circulation Research
JF - Circulation Research
IS - 5
ER -