Regulation of vascular type 1 angiotensin receptors by cytokines

Hiroyuki Sasamura, Yuichi Nakazato, Tomoko Hayashida, Yudai Kitamura, Matsuhiko Hayashi, Takao Saruta

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53 Citations (Scopus)

Abstract

Although various cytokines are known to be expressed in atherosclerotic lesions, it is not known how these cytokines affect receptors for the peptide hormone angiotensin II (Ang II). We therefore examined the effects of interleukin-1α (220 U/mL [10 ng/mL]), tumor necrosis factor-α (280 U/mL [100 ng/mL]), and interferon gamma (100 U/mL) on Ang II type 1 (AT,) receptors expressed in rat vascular smooth muscle cells. Treatment with interleukin-1α caused a 1.4- to 1.7-fold increase in AT, binding after 24 hours (P<.01) and a 2.3-fold increase in AT1 mRNA (P<.05). Tumor necrosis factor-α and interferon gamma did not cause a significant change in AT1 binding when administered alone but caused a 30% reduction in binding when administered together (P<.05). The maximal decrease in AT1 binding (60%, P<.01) was seen with the combination of interleukin-1α with tumor necrosis factor-α and interferon gamma. Although the upregulation of AT1 by interleukin-1α was unaffected by pretreatment of cells with N-monomethyl-L- arginine or indomethacin, downregulation of AT1 by interleukin-1α combined with tumor necrosis factor-α/interferon gamma was inhibited by N-monomethyl- L-arginine (P<.01). Interleukin-1α treatment enhanced Ang II-induced [3H]uridine incorporation, whereas treatment with interleukin-1α combined with tumor necrosis factor-α/interferon gamma attenuated Ang II-induced [3H]uridine and [3H]leucine incorporation. These results demonstrate that interleukin-1α upregulates AT1 receptors and enhances Ang II-stimulated hypertrophic responses. However, a combination of interleukin-1α with tumor necrosis factor-α and interferon gamma downregulates AT1 receptors by a nitric oxide-dependent mechanism and reduces Ang 11-stimulated trophic responses in vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalHypertension
Volume30
Issue number1
DOIs
Publication statusPublished - 1997 Jul

Keywords

  • Angiotensin
  • Cytokines
  • Interferons
  • Interleukin-1
  • Receptors
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Internal Medicine

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  • Cite this

    Sasamura, H., Nakazato, Y., Hayashida, T., Kitamura, Y., Hayashi, M., & Saruta, T. (1997). Regulation of vascular type 1 angiotensin receptors by cytokines. Hypertension, 30(1), 35-41. https://doi.org/10.1161/01.HYP.30.1.35