Xuejun Chen1, Wenzhi Han1, Yanfang Zhang1, Wenyu Cui2, Zhiyuan Pan1, Xin Jin1, Chaoliang Long3, Hai Wang4. 1. Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China. 2. Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China. 3. Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China. Electronic address: longchaoliang@sohu.com. 4. Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing 100039, China. Electronic address: wh9588@sina.com.
Abstract
AIMS: The endothelial molecular pathway of a new ATP-sensitive potassium channel (KATP) opener natakalim was investigated in mesenteric arterioles of rats. MAIN METHODS: A DMT wire myograph was used to evaluate the vasorelaxation effects of natakalim. Ca(2+) responses of endothelial cells induced by natakalim were measured by laser confocal fluorescence microscopy. NO assay kits and Western blotting were used. KEY FINDINGS: The new KATP opener natakalim significantly produced endothelium-dependent arteriolar dilation and increased endothelial cell intracellular calcium concentration ([Ca(2+)]i) as well as NO release, which could be inhibited by SB366791 and capsazepine, the specific TRPV1 blockers. Additionally, down-regulation of endothelial TRPV1 by RNA interference inhibited the Ca(2+) influx induced by natakalim. SIGNIFICANCE: These results suggest that endothelial KATP mediated natakalim-induced vasorelaxation through increasing [Ca(2+)]i and NO production. Activation of endothelial TRPV1 channels and subsequent Ca(2+) entry, and NO release at least partly contribute to endothelium-dependent vasorelaxation induced by natakalim.
AIMS: The endothelial molecular pathway of a new ATP-sensitive potassium channel (KATP) opener natakalim was investigated in mesenteric arterioles of rats. MAIN METHODS: A DMT wire myograph was used to evaluate the vasorelaxation effects of natakalim. Ca(2+) responses of endothelial cells induced by natakalim were measured by laser confocal fluorescence microscopy. NO assay kits and Western blotting were used. KEY FINDINGS: The new KATP opener natakalim significantly produced endothelium-dependent arteriolar dilation and increased endothelial cell intracellular calcium concentration ([Ca(2+)]i) as well as NO release, which could be inhibited by SB366791 and capsazepine, the specific TRPV1 blockers. Additionally, down-regulation of endothelial TRPV1 by RNA interference inhibited the Ca(2+) influx induced by natakalim. SIGNIFICANCE: These results suggest that endothelial KATP mediated natakalim-induced vasorelaxation through increasing [Ca(2+)]i and NO production. Activation of endothelial TRPV1 channels and subsequent Ca(2+) entry, and NO release at least partly contribute to endothelium-dependent vasorelaxation induced by natakalim.
Authors: Alla B Salmina; Yulia K Komleva; István A Szijártó; Yana V Gorina; Olga L Lopatina; Galina E Gertsog; Milos R Filipovic; Maik Gollasch Journal: Front Physiol Date: 2015-12-11 Impact factor: 4.566
Authors: Ivan Linares-Cervantes; Dagmar Kollmann; Toru Goto; Juan Echeverri; Johan Moritz Kaths; Matyas Hamar; Peter Urbanellis; Laura Mazilescu; Roizar Rosales; Claudia Bruguera; Fabiola Oquendo; Sujani Ganesh; Oyedele A Adeyi; Paul Yip; Nazia Selzner; Markus Selzner Journal: Transplant Direct Date: 2019-03-04