期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 900, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2021.174055
关键词
Norepinephrine; Norepinephrine transporter; Obstructive jaundice; Vascular hyporeactivity; Bile duct ligation; ?1-adrenoceptor
资金
- National Natural Science Foundation of China (Beijing, China) [81671082]
- Department of Science and Technology Program in Zhejiang Province (Zhejiang, China) [2018C37134]
- Health Commission of Zhejiang Province (Zhejiang, China) [2018KY855]
This study demonstrates that the NET inhibitor nisoxetine plays a protective role in BDL-induced vascular hyporeactivity in rats by increasing α1-adrenoceptor activation. This research suggests a potential therapeutic target for cardiovascular complications in patients with obstructive jaundice.
In patients with obstructive jaundice, the cardiovascular system exhibits hypotension and vascular hyporeactivity. Most norepinephrine is taken up through the neuronal norepinephrine transporter (NET), which is implicated in cardiovascular diseases. A previous study demonstrated that pharmacological NET inhibition could increase resting blood pressure. However, the role of NETs in vascular hyporeactivity induced by obstructive jaundice is poorly understood. This study used the NET inhibitor nisoxetine and a rat model of bile duct ligation (BDL) to investigate whether NET is associated with BDL-induced vascular hyporeactivity. Rats were injected with nisoxetine via the tail vein for 7 consecutive days after BDL. Samples of the superior cervical sympathetic ganglion (SCG) and thoracic aortic rings were processed for investigations. Our results showed that NET expression in the SCG was significantly increased after BDL. Nisoxetine prevented the augmentation of NET expression, increased ?1-adrenoceptor activation, and enhanced the weakened contractile responses of thoracic aortic rings after BDL. Our study demonstrates that nisoxetine plays a protective role in BDL-induced vascular hyporeactivity through increased ?1-adrenoceptor activation in rats.
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