左旋西孟旦
格列本脲
血管舒张
四乙基铵
钾通道
通道阻滞剂
四乙基氯化铵
内科学
医学
钾通道阻滞剂
血管平滑肌
药理学
麻醉
心脏病学
化学
内分泌学
心力衰竭
钾
钙
平滑肌
糖尿病
有机化学
作者
Chunwu Yang,Hongbing Qiu,Chan Wang,Yanlin Tang,Chengrui Zhang,Yanying Fan,Xiangying Jiao
出处
期刊:Journal of Cardiovascular Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2023-12-15
卷期号: (00)
标识
DOI:10.1097/fjc.0000000000001524
摘要
Abstract: Studies have examined the therapeutic effect of levosimendan on cardiovascular diseases such as heart failure, perioperative cardiac surgery, and septic shock, but the specific mechanism in mice remains largely unknown. This study aimed to investigate the relaxation mechanism of levosimendan in the thoracic aorta smooth muscle of mice. Levosimendan-induced relaxation of isolated thoracic aortic rings that were precontracted with norepinephrine (NE) or KCl was recorded in an endothelium-independent manner. Vasodilatation by levosimendan was not associated with the production of the endothelial relaxation factors NO and PGI 2 . The voltage-dependent K + channel (K V ) blocker (4-aminopyridine) and selective K Ca blocker (tetraethylammonium) had no effect on thoracic aortas treated with levosimendan, indicating that K V and K Ca channels may not be involved in the levosimendan-induced relaxation mechanism. Although the inwardly rectifying K + channel (K ir ) blocker (barium chloride) and the K ATP channel blocker (glibenclamide) significantly inhibited levosimendan-induced vasodilation in the isolated thoracic aorta, barium chloride had a much stronger inhibitory effect on levosimendan-induced vasodilation than glibenclamide, suggesting that levosimendan-induced vasodilation may be mediated by K ir channels. The vasodilation effect and expression of K ir 2.1 induced by levosimendan were further enhanced by the PKC inhibitor staurosporine. Extracellular calcium influx was inhibited by levosimendan without affecting intracellular Ca 2+ levels in the isolated thoracic aorta. These results suggest that K ir channels play a more important role than K ATP channels in regulating vascular tone in larger arteries and that the activity of the K ir channel is enhanced by the PKC pathway.
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