Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway.
10.4196/kjpp.2016.20.5.539
- Author:
Sujeong CHOI
1
;
Hyon Jo KWON
;
Hee Jung SONG
;
Si Wan CHOI
;
Harsha NAGAR
;
Shuyu PIAO
;
Saet Byel JUNG
;
Byeong Hwa JEON
;
Dong Woon KIM
;
Cuk Seong KIM
Author Information
1. Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea. cskim@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
Endothelial nitric oxide synthase;
Nafamostat mesilate;
Nitric oxide;
Vascular relaxation
- MeSH:
Animals;
Aorta;
Arginase;
Arginine;
Biological Availability;
Endothelial Cells;
Endothelium;
Human Umbilical Vein Endothelial Cells;
Mesylates*;
Nitric Oxide;
Nitric Oxide Synthase;
Nitric Oxide Synthase Type III;
Phosphorylation;
Rats;
Relaxation;
Serine Proteases;
Vasodilation*
- From:The Korean Journal of Physiology and Pharmacology
2016;20(5):539-545
- CountryRepublic of Korea
- Language:English
-
Abstract:
Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.
