Christensen F H, Hansen T, Stankevicius E, Buus N H, Simonsen U
Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
Br J Pharmacol. 2007 Jan;150(1):80-7. doi: 10.1038/sj.bjp.0706965. Epub 2006 Nov 27.
The present study investigated mechanisms underlying impaired endothelium-dependent vasodilatation elicited by elevating the intraluminal pressure in rat mesenteric small arteries.
Arterial segments (internal diameter 316+/-2 microm, n=86) were mounted in a pressure myograph. The effect of elevating pressure from 50 to 120 mmHg for 1 h before resetting it to 50 mmHg was studied on endothelium-dependent vasodilatation.
In arteries constricted with U46619 in the presence of indomethacin, shear stress generated by flow, evoked vasodilatation that was abolished by an inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (1 mM), whereas acetylcholine-induced vasodilatation was unchanged. After elevation of intraluminal pressure for 1 h and then resetting it to 50 mmHg, vasodilatation induced by shear stress and the NO donor, S-nitrosopenicillamine was inhibited, while vasodilatation induced by a guanylyl cyclase activator, BAY 412272, and acetylcholine was unaltered. Superoxide levels sensitive to polyethylene glycol superoxide dismutase were increased in segments exposed to elevated pressure. A superoxide scavenger, tempol (300 microM), a general endothelin receptor antagonist, SB 217242 and the selective ET(A) receptor antagonist, BQ 123 preserved shear stress-evoked vasodilatation.
The present study shows that transient exposure to an elevated intraluminal pressure selectively inhibits flow-evoked NO-mediated vasodilatation, probably through activation of endothelin receptors and increased formation of superoxide. In contrast, elevation of pressure did not affect the acetylcholine-evoked endothelium-derived hyperpolarizing factor type vasodilatation in mesenteric small arteries.
本研究探究了大鼠肠系膜小动脉管腔内压力升高引发内皮依赖性血管舒张受损的潜在机制。
将动脉段（内径316±2微米，n = 86）安装在压力肌动描记仪上。研究了在将压力从50 mmHg升高至120 mmHg并持续1小时后再将其重置为50 mmHg对内皮依赖性血管舒张的影响。
在吲哚美辛存在的情况下用U46619收缩的动脉中，由血流产生的剪切应力诱发血管舒张，而一氧化氮（NO）合酶抑制剂非对称二甲基精氨酸（1 mM）可消除这种舒张，而乙酰胆碱诱导的血管舒张则未改变。管腔内压力升高1小时后再将其重置为50 mmHg，剪切应力和NO供体S-亚硝基青霉胺诱导的血管舒张受到抑制，而鸟苷酸环化酶激活剂BAY 41-2272和乙酰胆碱诱导的血管舒张未改变。暴露于升高压力的动脉段中对聚乙二醇超氧化物歧化酶敏感的超氧化物水平升高。超氧化物清除剂tempol（300 microM）、通用内皮素受体拮抗剂SB 217242和选择性ET(A)受体拮抗剂BQ 123可保留剪切应力诱发的血管舒张。
本研究表明，短暂暴露于升高的管腔内压力会选择性抑制血流诱发的NO介导的血管舒张，可能是通过激活内皮素受体和增加超氧化物的形成。相比之下，压力升高并不影响肠系膜小动脉中乙酰胆碱诱发的内皮衍生超极化因子型血管舒张。
