Coxsackievirus B3 infection compromises endothelial-dependent vasodilation of coronary resistance arteries.
Coxsackievirus B3 infection compromises endothelial-dependent vasodilation of coronary resistance arteries.
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柯萨奇病毒 B3 感染会损害冠状动脉阻力动脉的内皮依赖性血管舒张。
DOI：
10.1097/00005344-200401000-00007
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发表时间：
2004
影响因子：
3
通讯作者：
Laher,Ismail
中科院分区：
文献类型：
--
作者：
Choy,JonathanC;Lui,AmyH;Moien-Afshari,Farzad;Wei,Kevin;Yanagawa,Bobby;McManus,BruceM;Laher,Ismail
柯萨奇病毒 B3 (CVB3) 介导的病毒性心肌炎导致冠状动脉功能障碍的机制尚不清楚。我们使用小鼠间隔冠状动脉的压力肌动描记法来确定 CVB3 感染对血管功能的早期和晚期影响。雄性CD-1小鼠（6-7周龄）感染CVB3（1.75×10 10 pfu，腹膜内）。对照小鼠注射 PBS。感染后3、7和42天处死小鼠，解剖室间隔动脉并安装在压力肌动描记器上。感染后 3 天和 7 天，CVB3 感染和假感染小鼠中压力诱导的肌原性张力相似。然而，与假手术对照组相比，感染 CVB3 的小鼠在感染后 42 天时，间隔动脉收缩至等于或小于 60 mm Hg 的压力增强。通过对乙酰胆碱 (1 nM–3 μM) 的反应来评估，在 CVB3 感染的小鼠中，激动剂诱导的血管舒张在早期时间点（第 3 天和第 7 天）没有改变。在稍后的时间点（第 42 天），CVB3 感染的小鼠中 ACh 诱导的血管舒张显着减少。波生坦 (Bosentan) 是一种 ET-1（ET A 和 ET B）受体拮抗剂，在 42 天感染小鼠中并没有完全改善乙酰胆碱诱导的血管舒张减少，表明 ET-1 不会导致血管功能障碍。通过对 KCl 的收缩或对硝普钠的扩张来测量平滑肌功能，在感染小鼠的早期和晚期时间点没有变化。然后进行免疫组织化学和 ET-1 免疫测定，以评估 CVB3 感染和假感染心脏中的 ET-1 水平。在假感染和 CVB3 感染的动物中，感染后 42 天的 ET-1 蛋白定位或水平没有差异。最后，进行原位杂交和 TUNEL 染色以评估 CVB3 感染心脏中的病毒定位和细胞死亡。冠状动脉内皮细胞中未检测到 CVB3 或 TUNEL 阳性。因此，CVB3诱导的心肌炎中冠状动脉阻力血管的内皮依赖性血管舒张的晚期损伤似乎并不涉及ET-1表达的改变，但可能继发于内皮刺激的NO分泌减少。
The mechanisms of coronary artery dysfunction in coxsackievirus B3 (CVB3)-mediated viral myocarditis are poorly understood. We used pressure myography of mouse septal coronary arteries to determine the early and late effects of CVB3 infection on vascular function. Male CD-1 mice (age 6–7 weeks) were infected with CVB3 (1.75× 10 10 pfu, ip). Control mice were injected with PBS. Mice were killed at 3, 7, and 42 days post infection, and the ventricular septal artery was dissected and mounted on a pressure myograph. Pressure-induced myogenic tone was similar in CVB3-infected and sham-infected mice at 3 and 7 days post infection. However, at 42 days post infection constriction of septal arteries to pressures equal to or less than 60 mm Hg was enhanced in CVB3-infected mice compared with sham controls. Agonist-induced vasodilation, as assessed by response to acetylcholine (1 nM–3 μM), was unaltered at early time points (days 3 and 7) in CVB3-infected mice. At later time points (day 42), there was a significant decrease in ACh-induced vasodilation in CVB3-infected mice. Bosentan, an ET-1 (ET A and ET B) receptor antagonist, did not completely ameliorate the reduced ACh-induced vasodilation in 42-day infected mice, indicating that ET-1 does not contribute to vascular dysfunction. Smooth muscle function, as measured by constriction to KCl or dilation to sodium nitroprusside, was unchanged in infected mice at early and late time points. Immunohistochemistry and ET-1 immunoassay were then performed to assess ET-1 levels in CVB3-and sham-infected hearts. There were no differences in ET-1 protein localization or levels at 42 days post infection in sham-and CVB3-infected animals. Finally, in situ hybridization and TUNEL staining were performed to assess viral localization and cell death in CVB3-infected hearts. There was no detectable CVB3 or TUNEL positivity in the endothelium of coronary arteries. Therefore, late impairment of endothelial-dependent vasorelaxation of coronary resistance vessels in CVB3-induced myocarditis does not appear to involve altered ET-1 expression but may be secondary to decreased stimulated NO secretion by the endothelium.