Bronquard Cécile, Maupoil Véronique, Arbeille Brigitte, Fetissof Franck, Findlay Ian, Cosnay Pierre, Freslon Jean-Louis
Université François-Rabelais, CNRS UMR 6542, 31 Avenue Monge, 37200 Tours, France.
Fundam Clin Pharmacol. 2007 Feb;21(1):55-65. doi: 10.1111/j.1472-8206.2006.00457.x.
The aim of this study was to investigate the in vitro vasomotor properties of rat extra-and intralobar pulmonary veins (PVs) related to their localization and to assess the modulatory role of endothelium on these properties. Segments from PVs were mounted in small vessel myograph and stretched at various diameters (D(10), D(20), D(30)) corresponding to intraluminal pressures of 10, 20 or 30 mmHg. At D(10) or D(20), contractile responses to phenylephrine, U46619 and angiotensin II of distal intralobar part of PVs were smaller compared with those of proximal extralobar part, but no longer different when distal part was stretched at D(30). When submitted to an NO donor, sodium nitroprusside, distal part of PV relaxed more strongly when stretched at D(30) compared with D(10). Acetylcholine and bradykinin were devoid of relaxing effect on distal parts stretched at D(10), but in contrast to acetylcholine, bradykinin slightly relaxed preparations stretched at D(30). Isoprenaline strongly relaxed PVs ( approximately 80% of initial precontraction), with the distal part exhibiting a higher sensitivity to the agonist compared with the proximal part. This relaxation was also observed with salbutamol and suppressed with ICI 118551, which is in favour of the involvement of beta(2)-adrenoceptors in this effect. Preincubation of the preparations with N(G)-nitro-l-arginine methyl ester (10(-4) m) and indomethacin (10(-5) m) did not modify the contractile responses to U46619, nor the relaxing response to isoprenaline, which support that endothelium does not appear to play a significant modulatory role in these responses. Histological and electron microscopical examinations of proximal and distal sections of the same vein show that the layers of smooth muscle cells and cardiomyocytes were thicker in the proximal compared with the distal part. This study shows that, because of morphological heterogeneity of the PVs, the site of dissection and the initial condition of tension can play a significant role upon the sensitivity and the magnitude of the responses to both contractile and relaxing agonists.
本研究的目的是探究大鼠肺叶外和肺叶内肺静脉(PVs)的体外血管舒缩特性与其定位的关系,并评估内皮对这些特性的调节作用。将PVs的节段安装在小血管肌动描记器中,并在对应于10、20或30 mmHg腔内压力的不同直径(D(10)、D(20)、D(30))下进行拉伸。在D(10)或D(20)时,与肺叶外近端部分相比,肺叶内PVs远端部分对去氧肾上腺素、U46619和血管紧张素II的收缩反应较小,但当远端部分在D(30)拉伸时,两者不再有差异。当给予一氧化氮供体硝普钠时,与在D(10)拉伸相比,在D(30)拉伸时PVs远端部分舒张更强。乙酰胆碱和缓激肽对在D(10)拉伸的远端部分没有舒张作用,但与乙酰胆碱不同的是,缓激肽对在D(30)拉伸的标本有轻微舒张作用。异丙肾上腺素能使PVs强烈舒张(约为初始预收缩的80%),与近端部分相比,远端部分对该激动剂表现出更高的敏感性。沙丁胺醇也观察到这种舒张作用,且被ICI 118551抑制,这支持β(2)-肾上腺素受体参与了这一作用。用N(G)-硝基-L-精氨酸甲酯(10(-4) m)和吲哚美辛(10(-5) m)对标本进行预孵育,既不改变对U46619的收缩反应,也不改变对异丙肾上腺素的舒张反应,这表明内皮在这些反应中似乎没有发挥显著的调节作用。对同一静脉近端和远端切片的组织学和电子显微镜检查表明,近端平滑肌细胞层和心肌细胞层比远端更厚。本研究表明,由于PVs的形态异质性,解剖部位和初始张力条件对收缩和舒张激动剂反应的敏感性和幅度可发挥重要作用。