ROLE OF PEPTIDASES IN BRADYKININ-INDUCED INCREASE IN VASCULAR-PERMEABILITY INVIVO
ROLE OF PEPTIDASES IN BRADYKININ-INDUCED INCREASE IN VASCULAR-PERMEABILITY INVIVO
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DOI：
10.1161/01.res.70.5.952
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发表时间：
1992-05-01
影响因子：
20.1
通讯作者：
RUBINSTEIN, I
中科院分区：
文献类型：
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作者：
TAN, Y;XIAO, PG;RUBINSTEIN, I
本研究的目的是探讨广泛分布于微循环中的中性内肽酶和血管紧张素转换酶在缓激肽诱导的仓鼠颊囊血管通透性增加中的作用。血管通透性的变化通过计数渗漏部位的数量和计算缓激肽灌流时荧光素异硫氰酸酯(FITC)-葡聚糖(分子质量，70000 d)的清除量来定量。缓激肽使FITC-葡聚糖的渗漏部位数量和清除量随浓度和时间的增加而增加。选择性、活性部位导向的中性内切酶抑制剂磷酰胺(1.0-mU-M)、硫胺(10.0-mU-M)和选择性血管紧张素转换酶抑制剂卡托普利(10.0-mU-M)均使缓激肽的量效曲线显著左移。在缓激肽(1.0-mU-M)和磷酰胺灌流期间，渗漏部位的数量从每0.11平方厘米17+/-2个显著增加到27+/-4个(平均+/-扫描电子显微镜，p<；0.05)，FITC-葡聚糖清除率从1.0+/-0.2显著增加到2.1+/-0.3ml/s×10(-6)。在缓激肽(1.0-mU-M)和卡托普利灌流期间，渗漏点数从每0.11cm2 10+/-2个显著增加到41+/-3个，FITC-葡聚糖清除率从0.8+/-0.3个显著增加到3.2+/-0.8ml/s×10(-6)个。在缓激肽(1.0-mU-M)和硫代巴比妥钠灌流期间，渗漏部位的数量从每0.11平方厘米15+/-3个显著增加到47+/-7个，FITC-葡聚糖清除从0.8+/-0.2个显著增加到4.7+/-0.6毫升/秒×10(-6)个。磷酰胺和卡托普利的充盈与缓激肽诱导的反应的相加效应有关。其他蛋白水解酶抑制剂对缓激肽诱导的血管通透性增加无明显影响。此外，磷酰胺和卡托普利不能增强腺苷(1.0-mU-M)诱导的渗漏部位形成的增加。我们得出结论，中性内肽酶和血管紧张素转换酶各自在调节缓激肽诱导的体内血管通透性增加中发挥重要作用。
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-mu-M) and thiorphan (10.0-mu-M) and the selective angiotensin I-converting enzyme inhibitor captopril (10.0-mu-M) each shifted the concentration-response curve to bradykinin significantly to the left. During suffusion with bradykinin (1.0-mu-M) 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 +/- O.3 ml/sec x 10(-6). During suffusion with bradykinin (1.0-mu-M) 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 x 10(-6). During suffusion with bradykinin (1.0-mu-M) 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 x 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-mu-M)-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.