期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 285, 期 1, 页码 H406-H417出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00021.2003
关键词
bradykinin; platelet-activating factor; inflammatory gaps; vascular endothelium; ML-7; myosin light chain kinase
资金
- NHLBI NIH HHS [HL-28607, HL-44485] Funding Source: Medline
We tested the hypothesis that acutely induced hyperpermeability is dependent on actin-myosin contractility by using individually perfused mesentery venules of pento-barbital-anesthetized rats. Venule hydraulic conductivity (L-p) was measured to monitor hyperpermeability response to the platelet-activating factor (PAF) 1-O-hexadecyl-2-acetylsnglycero-3-phosphocholine or bradykinin. Perfusion with PAF (10 nM) induced a robust transient high L-p [24.3 +/- 1.7 x 10(-7) cm/(s.cm H2O)] that peaked in 8.9 +/- 0.5 min and then returned toward control L-p [1.6 +/- 0.1 x 10(-7) cm/(s.cmH(2)O)]. Reconstruction of venular segments with the use of transmission electron microscopy of serial sections confirmed that PAF induces paracellular inflammatory gaps. Specific inhibition of myosin light chain kinase (MLCK) with 1-10 muM 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7) failed to block the PAF L-p response or change the time-to-peak L-p. ML-7 reduced baseline L-p 50% at 40 min of pretreatment. ML-7 also increased the rate of recovery from PAF hyperpermeability measured as the decrease of half-time of recovery from 4.8 +/- 0.7 to 3.2 +/- 0.3 min. Inhibition of myosin ATPase with 5-20 mM 2,3-butanedione 2-monoxime also failed to alter the hyperpermeability response to PAF. Similar results were found using ML-7 to modulate responses. These experiments indicate that an actin-myosin contractile mechanism modulated by MLCK does not contribute significantly to the robust initial increase in permeability of rat venular microvessels exposed to two common inflammatory mediators. The results are consistent with paracellular gap formation by local release of endothelial-endothelial cell adhesion structures in the absence of contraction by the actin-myosin network.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据