PRESSURE ENHANCES ENDOTHELIN-1 RELEASE FROM CULTURED HUMAN ENDOTHELIAL-CELLS

The effect of pure pressure without shear stress or stretch on the rel ease of endothelin-1 was investigated. Elevation of pressure significa ntly enhanced endothelin-1 release from cultured human umbilical vein endothelial cells. A calcium channel blocker, nifedipine, and a putati ve stretch-activated channel blocker, gadolinium, did not affect the p ressure-induced endothelin-1 increase. On the other hand, a phospholip ase C inhibitor, 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate and pro tein kinase C inhibitors, 1-5-(isoquinolinylsulfonyl)-2-methylpiperazi ne and chelerythrine, significantly inhibited the pressure-induced end othelin-1 increase. Moreover, pure pressure reduced basal nitric oxide release, while pretreatment with a nitric oxide synthase inhibitor, N -G-monomethyl-L-arginine, had no effect on the pressure-induced endoth elin-1 increase. In conclusion, our results show for the first time th at pressure enhances endothelin-1 release partially through activation of phospholipase C and protein kinase C in human endothelial cells.