(Hypertension. 1995;25:449-452.)
© 1995 American Heart Association, Inc.
Articles |
From the Departments of Internal Medicine and Pharmacology (T.N., R.K.), Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Correspondence to Toshio Nakaki, MD, PhD, Department of Pharmacology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160 Japan.
Abstract 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 C in human endothelial cells.
Key Words: endothelin-1 mechanoreception Ca2+ channel stretch pressure nitric oxide
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