Pressure enhances endothelin-1 release from cultured human endothelial cells.
The effect of pure pressure without shear stress or stretch on the release of endothelin-1 was investigated. Elevation of pressure significantly enhanced endothelin-1 release from cultured human umbilical vein endothelial cells. A calcium channel blocker, nifedipine, and a putative stretch-activated channel blocker, gadolinium, did not affect the pressure-induced endothelin-1 increase. On the other hand, a phospholipase C inhibitor, 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate, and protein kinase C inhibitors, 1-5-(isoquinolinylsulfonyl)-2-methylpiperazine and chelerythrine, significantly inhibited the pressure-induced endothelin-1 increase. Moreover, pure pressure reduced basal nitric oxide release, while pretreatment with a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, had no effect on the pressure-induced endothelin-1 increase. In conclusion, our results show for the first time that pressure enhances endothelin-1 release partially through activation of phospholipase C and protein kinase.
Hishikawa
K
K
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nakaki
T
T
Marumo
T
T
Suzuki
H
H
Kato
R
R
Saruta
T
T
D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology; D010812:Physical Stimulation; D011312:Pressure; D011493:Protein Kinase C / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D015220:Calcium Channels; D016232:Endothelins; D009569:Nitric Oxide; D011493:Protein Kinase C; D010738:Type C Phospholipases