Downregulation of vascular angiotensin II type 1 receptor by thyroid hormone

Kae Fukuyama, Toshihiro Ichiki, Kotaro Takeda, Tomotake Tokunou, Naoko Iino, Satoko Masuda, Minako Ishibashi, Kensuke Egashira, Hiroaki Shimokawa, Katsuya Hirano, Hideo Kanaide, Akira Takeshita

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Thyroid hormone has a broad effect on cardiovascular system. 3,3′,5-triiodo-L-thyronine (T3), a biologically active form of thyroid hormone, increases cardiac contractility. T3 causes arterial relaxation and reduction of systemic vascular resistance, resulting in an increase in cardiac output. However, the molecular mechanisms of vascular relaxation by T3 are incompletely characterized. We studied the effect of T3 on the angiotensin (Ang) II type 1 receptor (AT1R) expression in vascular smooth muscle cells. T3 dose-dependently decreased expression levels of AT1R mRNA, with a peak at 6 hours of stimulation. Binding assay using [125I] Sar1-Ile8-Ang II revealed that AT1R number was decreased by stimulation with T3 without changing the affinity to Ang II. T3 reduced calcium response of vascular smooth muscle cells to Ang II by 26%. AT1R promoter activity measured by luciferase assay was reduced by 50% after 9 hours of T3 administration. mRNA stability was also decreased by T3. Real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis revealed that AT1R mRNA and protein were downregulated in the aorta of T3-treated rats. These results suggest that T3 downregulates AT1R expression both at transcriptional and posttranscriptional levels, and attenuates biological function of Ang II. Our results suggest that downregulation of AT1R gene expression may play an important role for T3-induced vascular relaxation.

Original languageEnglish
Pages (from-to)598-603
Number of pages6
JournalHypertension
Volume41
Issue number3 I
DOIs
Publication statusPublished - Mar 1 2003

All Science Journal Classification (ASJC) codes

  • Internal Medicine

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