Microinjection of urotensin II into the rostral ventrolateral medulla increases sympathetic vasomotor tone via the GPR14/ERK pathway in rats
Microinjection of urotensin II into the rostral ventrolateral medulla increases sympathetic vasomotor tone via the GPR14/ERK pathway in rats
复制标题
尾加压素 II 显微注射到延髓头侧腹外侧可通过 GPR14/ERK 通路增加大鼠交感血管舒缩张力
DOI：
10.1038/s41440-020-0460-y
复制
发表时间：
2020-05-08
影响因子：
5.4
通讯作者：
Wu, Yuming
中科院分区：
文献类型：
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作者：
Cao, Ya-Kun;Guo, Qi;Wu, Yuming
本研究旨在揭示尾加压素II(UII)对延髓头端腹外侧区(RVLM)交感血管舒缩张力的影响。将UII(0.3、3和30 /L，50 nL)微量注入RVLm。测量血压(BP)、心率(HR)和肾交感神经活动(RSNA)以确定交感血管舒缩张力。向RVLM内微量注射药物后，同时记录BP、HR和RSNA。RVLm内微量注射UIi(0.3、3和30 /L，50 NL)可显著增加血压、心率和呼吸频率。UII受体GPR14的强效拮抗剂BIM23127(300 /L，50 NL)可阻断UII的作用。预先微量注射ERK抑制剂PD98059(25 μ/L，50 NL)可显著抑制UII的作用。预先注射N型钙通道阻断剂ω-芋螺毒素GVIA(50 /L，50 NL)可抑制UII的作用。本研究表明，RVLM内微量注射UII可显著增加交感血管舒张性，此作用由GPR14/ERK/N-型钙通道通路介导。UII可能成为自主神经系统调节的一个新的治疗靶点，特别是在高血压方面。
The present study aimed to reveal the effects of urotensin II (UII) on sympathetic vasomotor tone in the rostral ventrolateral medulla (RVLM). UII (0.3, 3, and 30 nmol/L, 50 nL) was microinjected into the RVLM. Blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to determine the sympathetic vasomotor tone. BP, HR, and RSNA were simultaneously recorded after drugs had been microinjected into the RVLM. Microinjection of UII (0.3, 3, and 30 nmol/L, 50 nL) into the RVLM significantly increased BP, HR, and RSNA. Pretreatment with BIM23127 (300 nmol/L, 50 nL), a potent antagonist of the UII receptor GPR14, abolished the effect of UII. Previous microinjection of PD98059 (25 μmol/L, 50 nL), an inhibitor of ERK, significantly suppressed the effects of UII. Preinjection of an inhibitor of the N-type Ca2+channel, ω-conotoxin GVIA (50 nmol/L, 50 nL), inhibited the effects of UII. The present study demonstrated that microinjection of UII into the RVLM significantly increased sympathetic vasomotor tone, which was mediated by the GPR14/ERK/N-type Ca2+channel pathway. UII may become a novel therapeutic target for autonomic nervous system regulation, especially in hypertension.