Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells

Keiichi Hishikawa, Toshio Nakaki, Takeshi Marumo, Matsuhiko Hayashi, Hiromichi Suzuki, Ryuichi Kato, Takao Saruta

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)


High blood pressure is one of the major risk factors for atherosclerosis. In this study, we examined the effects of pressure on cell proliferation and DNA synthesis in cultured rat vascular smooth muscle cells. Pressure without shear stress and stretch promotes cell proliferation and DNA synthesis in a pressure-dependent manner. Pressure-induced DNA synthesis was inhibited significantly by the phospholipase C (PLC) inhibitor 2-nitro-4- carboxyphenyl-N,N-diphenylcarbamate, the protein kinase C inhibitor H-7, 1- (5-isoquinolinylsulfonyl)-2-methylpiperazine, staurosporine, and the tyrosine kinase inhibitor ([3,4,5-trihydroxyphenyl]methylene)propanedinitrile. To clarify whether activation of PLC and calcium mobilization are involved in pressure-induced DNA synthesis, production of 1,4,5-inositol trisphosphate (IP3) and intracellular Ca2+ was measured. Pure pressure increased IP3 and intracellular Ca2+ in a pressure-dependent manner. The increases in both IP3 and intracellular Ca2+ were inhibited significantly by 2-nitro- 4-carboxyphenyl-N,N-diphenylcarbamate. This study demonstrates a novel cellular mechanism whereby pressure regulates DNA synthesis in vascular smooth muscle cells, possibly via activation of PLC and protein kinase C.

Original languageEnglish
Pages (from-to)1975-1980
Number of pages6
JournalJournal of Clinical Investigation
Issue number5
Publication statusPublished - 1994 May
Externally publishedYes


  • 1,4,5-inositol trisphosphate
  • Ca
  • atherosclerosis
  • mechanoreception
  • phospholipase C

ASJC Scopus subject areas

  • General Medicine


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