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埃拉贝拉通过 BK、K 和 K 通道使大鼠肺动脉和气管松弛。

Elabela relaxes rat pulmonary artery and trachea via BK, K, and K channels.

机构信息

Bursa Uludag University Medicine School, Physiology Department, Bursa, Turkey.

出版信息

Prostaglandins Other Lipid Mediat. 2023 Aug;167:106735. doi: 10.1016/j.prostaglandins.2023.106735. Epub 2023 Apr 12.

DOI:10.1016/j.prostaglandins.2023.106735
PMID:37059294
Abstract

OBJECTIVE

Elabela is a newly discovered peptide hormone. This study aimed to determine the functional effects and mechanisms of action of elabela in rat pulmonary artery and trachea.

MATERIALS AND METHODS

Vascular rings isolated from the pulmonary arteries of male Wistar Albino rats were placed in chambers in the isolated tissue bath system. The resting tension was set to 1 g. After the equilibration period, the pulmonary artery rings were contracted with 10 M phenylephrine. Once a stable contraction was achieved, elabela was applied cumulatively (10-10 M) to the vascular rings. To determine the vasoactive effect mechanisms of elabela, the specified experimental protocol was repeated after the incubation of signaling pathway inhibitors and potassium channel blockers. The effect and mechanisms of action of elabela on tracheal smooth muscle were also determined by a similar protocol.

RESULTS

Elabela exhibited a concentration-dependent relaxation in the precontracted rat pulmonary artery rings (p < .001). Maximal relaxation level was 83% (pEC: 7.947 CI95(7.824-8.069)). Removal of the endothelium, indomethacin incubation, and dideoxyadenosine incubation significantly decreased the vasorelaxant effect levels of elabela (p < .001). Elabela-induced vasorelaxation levels were significantly reduced after iberiotoxin, glyburide, and 4-Aminopyridine administrations (p < .001). L-NAME, methylene blue, apamin, TRAM-34, anandamide, and BaCl administrations did not cause a significant change in the vasorelaxant effect level of elabela (p = 1.000). Elabela showed a relaxing effect on precontracted tracheal rings (p < .001). Maximal relaxation level was 73% (pEC: 6.978 CI95(6.791-7.153)). The relaxant effect of elabela on tracheal smooth muscle was decreased significantly after indomethacin, dideoxyadenosine, iberiotoxin, glyburide, and 4-Aminopyridine incubations (p < .001).

CONCLUSIONS

Elabela exerted a prominent relaxant effect in the rat pulmonary artery and trachea. Intact endothelium, prostaglandins, cAMP signaling pathway, and potassium channels (BK, K, and K channels) are involved in the vasorelaxant effect of elabela. Prostaglandins, cAMP signaling pathway, BK channels, K channels, and K channels also contribute to elabela-induced tracheal smooth muscle relaxant effect.

摘要

目的

Elabela 是一种新发现的肽激素。本研究旨在确定 Elabela 在大鼠肺动脉和气管中的功能作用和作用机制。

材料和方法

将雄性 Wistar 白化大鼠的肺动脉血管环置于离体组织浴系统的腔室内。静息张力设定为 1g。在平衡期后,用 10 M 苯肾上腺素收缩肺动脉环。一旦达到稳定收缩,就将 Elabela 累积(10-10 M)应用于血管环。为了确定 Elabela 的血管活性作用机制,在孵育信号通路抑制剂和钾通道阻滞剂后重复指定的实验方案。还通过类似的方案确定 Elabela 对气管平滑肌的作用和作用机制。

结果

Elabela 在预收缩的大鼠肺动脉环中表现出浓度依赖性舒张(p <.001)。最大舒张水平为 83%(pEC:7.947 CI95(7.824-8.069))。去除内皮、吲哚美辛孵育和二脱氧腺苷孵育显著降低了 Elabela 的血管舒张作用水平(p <.001)。伊比替肟、格列本脲和 4-氨基吡啶给药后,Elabela 诱导的血管舒张水平显著降低(p <.001)。L-NAME、亚甲蓝、阿帕米、TRAM-34、大麻素和 BaCl 给药不会导致 Elabela 的血管舒张作用水平发生显著变化(p = 1.000)。Elabela 对预收缩的气管环表现出舒张作用(p <.001)。最大舒张水平为 73%(pEC:6.978 CI95(6.791-7.153))。吲哚美辛、二脱氧腺苷、伊比替肟、格列本脲和 4-氨基吡啶孵育后,Elabela 对气管平滑肌的舒张作用显著降低(p <.001)。

结论

Elabela 对大鼠肺动脉和气管表现出明显的舒张作用。完整的内皮、前列腺素、cAMP 信号通路和钾通道(BK、K 和 K 通道)参与了 Elabela 的血管舒张作用。前列腺素、cAMP 信号通路、BK 通道、K 通道和 K 通道也有助于 Elabela 诱导的气管平滑肌舒张作用。

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