Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes

Maria Alícia Carrillo-Sepúlveda, Graziela S. Ceravolo, Zuleica Bruno Fortes, Maria Helena Carvalho, Rita C. Tostes, Francisco R. Laurindo, R Clinton Webb, Maria Luiza M. Barreto-Chaves

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Aims Thyroid hormone (TH) rapidly relaxes vascular smooth muscle cells (VSMCs). However, the mechanisms involved in this effect remain unclear. We hypothesize that TH-induced rapid vascular relaxation is mediated by VSMC-derived nitric oxide (NO) production and is associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway.Methods and results NO levels were determined using a NO-specific fluorescent dye (DAF-2) and nitrite (NO2) levels. Expression of NO synthase (NOS) isoforms and proteins of the PI3K/Akt pathway was determined by both western blotting and immunocytochemistry. Myosin light chain (MLC) phosphorylation levels were also investigated by western blotting. Exposure of cultured VSMCs from rat thoracic aortas to triiodothyronine (T3) resulted in a significant decrease of MLC phosphorylation levels. T3 also induced a rapid increase in Akt phosphorylation and increased NO production in a dose-dependent manner (0.001-1 M). VSMCs stimulated with T3 for 30 min showed an increase in the expression of all three NOS isoforms and augmented NO production, effects that were prevented by inhibitors of PI3K. Vascular reactivity studies showed that vessels treated with T3 displayed a decreased response to phenylephrine, which was reversed by NOS inhibition. These data suggest that T3 treatment induces greater generation of NO both in aorta and VSMCs and that this phenomenon is endothelium independent. In addition, these findings show for the first time that the PI3K/Akt signalling pathway is involved in T3-induced NO production by VSMCs, which occurs with expressive participation of inducible and neuronal NOS.Conclusion Our data strongly indicate that T3 causes NO-dependent rapid relaxation of VSMC and that this effect is mediated by the PI3K/Akt signalling pathway.

Original languageEnglish (US)
Pages (from-to)560-570
Number of pages11
JournalCardiovascular Research
Volume85
Issue number3
DOIs
StatePublished - Feb 1 2010

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Phosphatidylinositol 3-Kinases
Thyroid Hormones
Muscle Cells
Blood Vessels
Vascular Smooth Muscle
Nitric Oxide
Smooth Muscle Myocytes
Nitric Oxide Synthase
Myosin Light Chains
Phosphorylation
Protein Isoforms
Western Blotting
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-akt
Triiodothyronine
Phenylephrine
Nitrites
Thoracic Aorta
Fluorescent Dyes
Endothelium

Keywords

  • Nitric oxide
  • Non-genomic actions
  • PI3K/Akt pathway
  • Relaxation
  • Thyroid hormone
  • Vascular smooth muscle cell

ASJC Scopus subject areas

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

Cite this

Carrillo-Sepúlveda, M. A., Ceravolo, G. S., Fortes, Z. B., Carvalho, M. H., Tostes, R. C., Laurindo, F. R., ... Barreto-Chaves, M. L. M. (2010). Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. Cardiovascular Research, 85(3), 560-570. https://doi.org/10.1093/cvr/cvp304

Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. / Carrillo-Sepúlveda, Maria Alícia; Ceravolo, Graziela S.; Fortes, Zuleica Bruno; Carvalho, Maria Helena; Tostes, Rita C.; Laurindo, Francisco R.; Webb, R Clinton; Barreto-Chaves, Maria Luiza M.

In: Cardiovascular Research, Vol. 85, No. 3, 01.02.2010, p. 560-570.

Research output: Contribution to journalArticle

Carrillo-Sepúlveda, MA, Ceravolo, GS, Fortes, ZB, Carvalho, MH, Tostes, RC, Laurindo, FR, Webb, RC & Barreto-Chaves, MLM 2010, 'Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes', Cardiovascular Research, vol. 85, no. 3, pp. 560-570. https://doi.org/10.1093/cvr/cvp304
Carrillo-Sepúlveda MA, Ceravolo GS, Fortes ZB, Carvalho MH, Tostes RC, Laurindo FR et al. Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. Cardiovascular Research. 2010 Feb 1;85(3):560-570. https://doi.org/10.1093/cvr/cvp304
Carrillo-Sepúlveda, Maria Alícia ; Ceravolo, Graziela S. ; Fortes, Zuleica Bruno ; Carvalho, Maria Helena ; Tostes, Rita C. ; Laurindo, Francisco R. ; Webb, R Clinton ; Barreto-Chaves, Maria Luiza M. / Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. In: Cardiovascular Research. 2010 ; Vol. 85, No. 3. pp. 560-570.
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AU - Carvalho, Maria Helena

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