5-羟色胺2受体在猪冠状动脉球囊损伤后慢性内皮功能障碍中的作用。

Involvement of 5-HT2 receptors in chronic endothelial dysfunction after balloon injury of porcine coronary arteries.

作者信息

Shibano T, Vanhoutte P M

机构信息

Department of Medicine, Baylor College of Medicine, Houston, TX 77030.

出版信息

Circulation. 1994 Apr;89(4):1776-85. doi: 10.1161/01.cir.89.4.1776.

DOI:10.1161/01.cir.89.4.1776

PMID:8149543

Abstract

BACKGROUND

Endothelium-dependent, pertussis toxin-sensitive relaxation to 5-hydroxytryptamine (5-HT) is impaired selectively after balloon injury of porcine coronary artery, followed by regeneration of the endothelial cells. The present study was designed to test the hypothesis that 5-HT, released from aggregating platelets, affects the progression of the endothelial dysfunction.

METHODS AND RESULTS

Yorkshire pigs were assigned randomly to three groups: control group (standard diet), denudation group (high-cholesterol diet plus balloon denudation of the endothelium of coronary artery under fluoroscopy), and DV-7028-treated group (denudation group plus chronic treatment with the selective 5-HT2 receptor antagonist DV-7028, given from the first day on after balloon denudation). Four weeks after the denudation, quantitative angiography revealed that 5-HT injected into the coronary artery decreased the luminal diameter of the left anterior descending coronary artery at the denuded site in the denudation group but not in the control or the DV-7028-treated group. Then, animals were killed so we could study the endothelium-dependent responses of their coronary arteries in conventional organ chambers. The arteries from the denudation group exhibited less relaxation to 5-HT and sodium fluoride (a stimulant of G proteins) than those of the control group. Relaxations to 5-HT and sodium fluoride were greater in arteries from the DV-7028-treated group than in those from the denudation group. In contrast, the endothelium-dependent, pertussis toxin-insensitive relaxations to bradykinin and thrombin and the endothelium-independent relaxations to sodium nitroprusside and isoproterenol were not affected significantly by chronic treatment with DV-7028.

CONCLUSIONS

These results suggest that 5-HT2 receptors are involved in the chronic progression of endothelial dysfunction after balloon denudation in the porcine coronary artery.

摘要

背景

猪冠状动脉球囊损伤后，内皮依赖性、百日咳毒素敏感的对5-羟色胺（5-HT）的舒张功能选择性受损，随后内皮细胞再生。本研究旨在验证以下假说：聚集血小板释放的5-HT会影响内皮功能障碍的进展。

方法与结果

约克夏猪被随机分为三组：对照组（标准饮食）、剥脱组（高胆固醇饮食加荧光透视下冠状动脉内皮球囊剥脱）和DV-7028治疗组（剥脱组加从球囊剥脱后第一天开始用选择性5-HT2受体拮抗剂DV-7028进行慢性治疗）。剥脱四周后，定量血管造影显示，向冠状动脉内注射5-HT会使剥脱组剥脱部位的左前降支冠状动脉管腔直径减小，但对照组和DV-7028治疗组未出现这种情况。然后，处死动物以便我们在传统器官腔室中研究其冠状动脉的内皮依赖性反应。与对照组相比，剥脱组的动脉对5-HT和氟化钠（一种G蛋白刺激剂）的舒张反应较小。DV-7028治疗组动脉对5-HT和氟化钠的舒张反应大于剥脱组。相比之下，对缓激肽和凝血酶的内皮依赖性、百日咳毒素不敏感的舒张反应以及对硝普钠和异丙肾上腺素的非内皮依赖性舒张反应不受DV-7028慢性治疗的显著影响。