Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway.
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.
Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Sujeong
S
Choi
Department of Neurosurgery, Regional Cerebrovascular Center, Chungnam National University Hospital, Daejeon 35015, Korea.
Hyon-Jo
HJ
Kwon
Department of Neurology, Chungnam National University Hospital, Daejeon 35015, Korea.
Hee-Jung
HJ
Song
Division of Cardiology, Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon 35015, Korea.
Si Wan
SW
Choi
Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Harsha
H
Nagar
Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Shuyu
S
Piao
Department of Endocrinology, Chungnam National University Hospital, Daejeon 35015, Korea.
Saet-Byel
SB
Jung
Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Byeong Hwa
BH
Jeon
Department of Anatomy & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Dong Woon
DW
Kim
Department of physiology & BK21Plus CNU Integrative Biomedical Education Initiative, School of Medicine, Chungnam National University, Daejeon 35015, Korea.
Cuk-Seong
CS
Kim
Endothelial nitric oxide synthase; Nafamostat mesilate; Nitric oxide; Vascular relaxation