Hypoxia and high glucose upregulate AT1 receptor expression and potentiate ANG II-induced proliferation in VSM cells

Chhinder P. Sodhi, Yashpal S. Kanwar, Atul Sahai

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the effect of hypoxia and high glucose (HG) on ANG II type 1 (AT1) receptor expression and proliferation in cultured vascular smooth muscle (VSM) cells. Exposure of quiescent cells to hypoxia in a serum-free DME-Ham's F-12 medium for 6-24 h induced a progressive increase in AT1 mRNA expression. Exposure of cells to 24 h of hypoxia also resulted in a significant increase in ANG II receptor binding as assessed with 125I-labeled ANG II. Treatment with ANG II (1 μM) for 24 h under normoxic conditions caused an ∼1.5-fold increase in both DNA synthesis and cell number, which was enhanced to ∼3.0-fold under hypoxic conditions. An AT1 receptor antagonist (losartan, 10 μM) blocked the ANG II-induced increase in DNA synthesis under both normoxic and hypoxic conditions. Incubations in HG medium (25 mM) for 12-24 h under normoxic conditions induced an ∼2.5-fold increase in AT1 mRNA levels, which was markedly enhanced by hypoxia to ∼5.5-fold at 12 h and ∼8.5-fold at 24 h. ANG II under HG-normoxic conditions caused a complete downregulation of AT1 expression, which was prevented by hypoxia. These results demonstrate an upregulation of AT1 receptor expression by hypoxia and HG in cultured VSM cells and suggest a mechanism for enhanced ANG II-induced VSM cell proliferation and the development of atherosclerosis in diabetes.

Original languageEnglish (US)
Pages (from-to)H846-H852
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number3 53-3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

Keywords

  • Angiotensin II receptor
  • Cell growth
  • Chronic hypoxia
  • Diabetes
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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