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The Mediation of Central Cyclooxygenase and Lipoxygenase Pathways in Orexin-Induced Cardiovascular Effects
Brain Research ( IF 2.9 ) Pub Date : 2021-01-04 , DOI: 10.1016/j.brainres.2020.147239
Burcin Altinbas 1 , Gokcen Guvenc-Bayram 2 , Murat Yalcin 2
Affiliation  

Previously it was reported that central orexin (OX) and arachidonic acid (AA) signaling pathways played an active role in the control of the cardiovascular system. It was also reported that they have exhibited their cardiovascular control role by using similar central or peripheral mechanisms. However, there has been no study demonstrating the interaction between OX and AA signaling pathways in terms of cardiovascular control. The current study was designed to investigate the possible mediation of the central cyclooxygenase (COX) and lipoxygenase (LOX) pathways in OX-induced cardiovascular effects in the rats.

Intracerebroventricular injection of OX increased blood pressure and heart rate in a dose-dependent manner in normotensive male Sprague Dawley rats. Moreover, the microdialysis study revealed that intracerebroventricular injected OX caused a time-dependent increase in the extracellular total prostaglandin concentrations in the posterior hypothalamus. Interestingly, central pretreatment with a non-selective COX inhibitor, ibuprofen, or a non-selective LOX inhibitor, nordihydroguaiaretic acid, partially reversed pressor and tachycardic cardiovascular responses evoked by central administration of OX.

In summary, our findings show that the central treatment with OX causes pressor and tachycardic cardiovascular responses along with an increase in posterior hypothalamic extracellular total prostaglandin concentrations. Furthermore, our results also demonstrate that central COX and LOX pathways mediate, at least in part, centrally administered OX-evoked pressor and tachycardic responses, as well.



中文翻译:

食欲素诱导的心血管效应中中枢环氧合酶和脂氧合酶通路的介导

此前有报道称,中枢食欲素 (OX) 和花生四烯酸 (AA) 信号通路在心血管系统的控制中发挥了积极作用。据报道,它们通过使用类似的中枢或外周机制发挥了其心血管控制作用。然而,没有研究证明 OX 和 AA 信号通路在心血管控制方面的相互作用。目前的研究旨在调查中枢环氧合酶 (COX) 和脂加氧酶 (LOX) 通路在 OX 诱导的大鼠心血管效应中的可能介导。

在血压正常的雄性 Sprague Dawley 大鼠中,脑室内注射 OX 以剂量依赖性方式增加血压和心率。此外,微透析研究表明,脑室内注射 OX 导致下丘脑后部细胞外总前列腺素浓度随时间增加。有趣的是,使用非选择性 COX 抑制剂布洛芬或非选择性 LOX 抑制剂去甲二氢愈创木酸进行中枢预处理,部分逆转了由中枢给药 OX 引起的升压和心动过速心血管反应。

总之,我们的研究结果表明,用 OX 进行中枢治疗会引起升压和心动过速心血管反应,同时会增加下丘脑后部细胞外总前列腺素浓度。此外,我们的结果还表明,中枢 COX 和 LOX 通路也至少部分介导中枢给药的 OX 诱发的升压和心动过速反应。

更新日期:2021-01-04
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