Department of Periodontology, School of Dentistry, University of Copenhagen, Denmark.
Vascul Pharmacol. 2010 Nov-Dec;53(5-6):250-7. doi: 10.1016/j.vph.2010.09.006. Epub 2010 Oct 1.
The purpose of our study was to examine if lipopolysaccharide (LPS) from Porphyromonas gingivalis (P.g.) modifies the vasomotor responses to Endothelin-1 (ET-1) and Sarafotoxin 6c (S6c) in rat coronary arteries. The arteries were studied directly or following organ culture for 24 h in absence and presence of 2.5EU/ml LPS. The contractile responses of coronary arteries were investigated by using the selective ETB receptor agonist S6c (1 pM-0.3 μM) and ET-1 (1 pM-0.3 μM). The functional studies demonstrated an augmented contractile response only to S6c in isolated rat coronary arteries after organ culture (with or without LPS). These contractile responses by S6c were blocked by the selective ETB receptor antagonist BQ788 in both vessel groups. The augmented contractile response to S6c was supported by immunohistochemistry, where a significant increase in fluorescence intensity for ETB receptors in smooth muscle cells was observed after organ culture. The presence of LPS in the culture medium significantly increased the sensitivity of endothelium-intact coronary artery to S6c as compared to endothelium-denuded segments. Our results showed a significant increase in both ETB receptor protein levels and S6c-induced maximal contraction in coronary arteries upon 24 h of organ culture, which was further sensitized by LPS.
我们的研究目的是探讨牙龈卟啉单胞菌(P.g.)脂多糖(LPS)是否改变内皮素-1(ET-1)和沙福毒素 6c(S6c)对大鼠冠状动脉血管舒缩反应的影响。将动脉直接研究或在 24 小时无和存在 2.5EU/ml LPS 的情况下进行器官培养后进行研究。通过使用选择性 ETB 受体激动剂 S6c(1 pM-0.3 μM)和 ET-1(1 pM-0.3 μM)研究冠状动脉的收缩反应。功能研究表明,在器官培养后(有或没有 LPS),分离的大鼠冠状动脉中仅对 S6c 的收缩反应增强。两种血管组中,S6c 的这种收缩反应均被选择性 ETB 受体拮抗剂 BQ788 阻断。S6c 的收缩反应增强得到免疫组织化学的支持,其中在器官培养后平滑肌细胞中 ETB 受体的荧光强度显著增加。与去内皮段相比,培养基中 LPS 的存在显著增加了完整内皮冠状动脉对 S6c 的敏感性。我们的结果表明,在器官培养 24 小时后,冠状动脉中 ETB 受体蛋白水平和 S6c 诱导的最大收缩均显著增加,LPS 进一步使这种敏感性增加。