Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells

Gang Liu, Hirofumi Hitomi, Naohisa Hosomi, Bai Lei, Nicolas Pelisch, Daisuke Nakano, Hideyasu Kiyomoto, Hong Ma, Akira Nishiyama

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Angiotensin II (AngII) stimulates vascular smooth muscle cell (VSMC) proliferation; however, the effect of AngII on cell proliferation in the presence of mechanical force is not clear. We investigated the mechanism of AngII-induced cell proliferation mediated by mechanical stretch in VSMCs of both normotensive and hypertensive rats. VSMCs obtained from the thoracic aortas of 8-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were stretched by a Flex culture system. Mechanical stretch significantly upregulated protein expression of AngII type 1 (AT 1) receptor, epidermal growth factor (EGF) receptor and mitogen-activated protein kinase phosphatase-1 in both SHR and WKY VSMCs; however, there was no significant difference in these changes between the cells from SHR and WKY. Mechanical stretch attenuated AngII-induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, ERK kinase (MEK) and EGF receptor; it also attenuated 3 H thymidine incorporation and cell proliferation in VSMC of WKY. In contrast, the effects of AngII were augmented by mechanical stretch in VSMC of SHR. AngII-induced ERK 1/2 phosphorylation and cell proliferation in SHR were inhibited by pretreatment with an AT 1 receptor blocker, candesartan and an inhibitor of MEK, PD98059. Moreover, pretreatment with an EGF receptor tyrosine kinase inhibitor, AG1478, also blocked upregulation of AngII-induced ERK 1/2 phosphorylation induced by stretch in SHR VSMCs. This study demonstrates that mechanical stretch augments SHR VSMC proliferation through an AT 1 /EGF receptor/ERK-dependent pathway. These findings may provide new insights into the signaling mechanisms whereby AngII exerts its growth-promoting effects on vasculature in a hypertensive state.

Original languageEnglish
Pages (from-to)1250-1257
Number of pages8
JournalHypertension Research
Volume33
Issue number12
DOIs
Publication statusPublished - 2010 Dec

Keywords

  • angiotensin II
  • epidermal growth factor receptor
  • mechanical stretch
  • spontaneously hypertensive rats
  • vascular smooth muscle cell

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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