Effects of endothelin receptor antagonists on bradykinin-induced increases in macromolecular efflux.
Effects of endothelin receptor antagonists on bradykinin-induced increases in macromolecular efflux.
复制标题
内皮素受体拮抗剂对缓激肽诱导的大分子流出增加的影响。
DOI：
10.1007/bf01535261
复制
发表时间：
1994
期刊：
影响因子：
5.1
通讯作者：
Rubinstein,I
中科院分区：
文献类型：
--
作者：
Mayhan,WG;Rubinstein,I
本研究的目的是确定内皮素受体拮抗剂在体内对激动剂诱导的仓鼠颊囊大分子渗出增加的影响。我们使用活体荧光显微镜和异硫氰酸荧光素葡聚糖(FITC-葡聚糖；摩尔质量分数=70K)来观察在应用内皮素受体抑制剂(ETABs和ETA)前后，缓激肽和内皮素对毛细血管后小静脉外渗的影响。通过计算静脉渗漏部位的数量来量化大分子渗出的增加。缓激肽(0.5和1.0μM)和内皮素-1(0.0 1和0.1 nM)可剂量依赖性地增加PD 142893(ETA拮抗剂)的渗漏部位数和灌注量，而PD 147953和BQ-12 3(ETA拮抗剂)可显著降低缓激肽和内皮素诱导的反应。在存在内皮素受体拮抗作用的情况下，向过熔液中添加钙可恢复缓激肽诱导的静脉渗漏部位的增加。因此，本研究的结果表明，内皮素受体拮抗剂可阻断缓激肽和内皮素诱导的毛细血管后小静脉大分子外流增加。内皮素受体拮抗剂的作用机制似乎与抑制ETA受体有关，而ETA受体反过来又改变了跨静脉内皮细胞的钙动员。
The goal of this study was to determine the effects of endothelin receptor antagonists on agonist-induced increases in macromolecular extravasation in the hamster cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt=70 K) to examine extravasation from postcapillary venules in response to bradykinin and endothelin before and following application of inhibitors of endothelin receptors (ETABand ETA). Increases in extravasation of macromolecules were quantitated by counting the number of venular leaky sites. Bradykinin (0.5 and 1.0μM) and endothelin-1 (0.01 and 0.1 nM) produced a dose-related increase in the number of venular leaky sites and superfusion of PD 142893 (ETABantagonist), and PD 147953 and BQ-123 (ETAantagonists) significantly decreased bradykinin- and endothelin-induced responses. Addition of calcium to the superfusate restored bradykinin-induced increases in venular leaky sites in the presence of endothelin receptor antagonism. Thus, the findings of the present study suggest that endothelin receptor antagonists abrogate bradykinin- and endothelin-induced increases in macromolecular efflux from postcapillary venules. The mechanism for the effects of endothelin receptor antagonists appears to be related to inhibition of the ETAreceptor which, in turn, alters the mobilization of calcium across venular endothelium.