Downregulation of Angiotensin II Type 1 Receptor Gene Transcription by Nitric Oxide

Toshihiro Ichiki, Makoto Usui, Makoto Kato, Yuko Funakoshi, Kiyoko Ito, Kensuke Egashira, Akira Takeshita

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Abstract

Nitric oxide (NO) plays an important role not only in the regulation of blood vessel tone, but also in the growth of vascular smooth muscle cells (VSMC). The precise mechanism involved in the inhibition of VSMC growth by NO is not known. To further explore the effect of NO on VSMC growth, we examined the effect of NO on the expression of angiotensin II type 1 receptor (AT1 -R) that is important for hypertrophy and hyperplasia of VSMC. S-nitroso acetyl DL-penicillamine (SNAP; 200 micro mol/L), a potent NO donor, suppressed expression level of AT1 -R mRNA by 90% and AT1 -R number by 60% after 24 hours of stimulation. The suppressive effect was dose-dependent. Actinomycin D, which is an inhibitor of gene transcription, did not affect the decrease of AT1 -R mRNA by NO. Cyclic guanosine monophosphate (cGMP) analogue, 8 bromo-cGMP, did not affect AT1 -R mRNA level. Deletion mutants of the promoter region of rat AT1 a-R gene were fused to luciferase reporter gene and introduced to VSMC. Transfected cells were stimulated with SNAP, and luciferase activity was measured. Inhibitory effect of NO was still observed in the shortest deletion mutant that contained 61 bp upstream from transcription start site. In this DNA segment, two DNA binding protein were observed by gel mobility shift assay, and one of these binding proteins was decreased on stimulation by NO. NO downregulates AT (1) -R gene expression independently of cGMP. A DNA binding protein that binds to the proximal promoter region of AT1 -R gene may be responsible for this inhibitory effect. The inhibition of AT1 -R gene expression may be implicated in the anti-atherogenic property of NO. (Hypertension. 1998;31[part 2]:342-348.).

Original languageEnglish
Pages (from-to)342-348
Number of pages7
JournalHypertension
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1998

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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    Ichiki, T., Usui, M., Kato, M., Funakoshi, Y., Ito, K., Egashira, K., & Takeshita, A. (1998). Downregulation of Angiotensin II Type 1 Receptor Gene Transcription by Nitric Oxide. Hypertension, 31(1), 342-348. https://doi.org/10.1161/01.hyp.31.1.342