Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism

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

Research output: Contribution to journalArticle

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Abstract

Hyperthyroidism is characterized by increased vascular relaxation and decreased vascular contraction and is associated with augmented levels of triiodothyronine (T3) that contribute to the diminished systemic vascular resistance found in this condition. T3 leads to augmented NO production via PI3K/Akt signaling pathway, which in turn causes vascular smooth muscle cell (VSMC) relaxation; however, the underlying mechanisms involved remain largely unknown. Evidence from human and animal studies demonstrates that the renin-angiotensin system (RAS) plays a crucial role in vascular function and also mediates some of cardiovascular effects found during hyperthyroidism. Thus, in this study, we hypothesized that type 2 angiotensin II receptor (AT2R), a key component of RAS vasodilatory actions, mediates T3 induced-decreased vascular contraction. Marked induction of AT2R expression was observed in aortas from T3-induced hyperthyroid rats (Hyper). These vessels showed decreased protein levels of the contractile apparatus: α-actin, calponin and phosphorylated myosin light chain (p-MLC). Vascular reactivity studies showed that denuded aortic rings from Hyper rats exhibited decreased maximal contractile response to angiotensin II (AngII), which was attenuated in aortic rings pre-incubated with an AT2R blocker. Further study showed that cultured VSMC stimulated with T3 (0.1 μmol/L) for 24 hours had increased AT2R gene and protein expression. Augmented NO levels and decreased p-MLC levels were found in VSMC stimulated with T3, both of which were reversed by a PI3K/Akt inhibitor and AT2R blocker. These findings indicate for the first time that the AT2R/Akt/NO pathway contributes to decreased contractile responses in rat aorta, promoted by T3, and this mechanism is independent from the endothelium.

Original languageEnglish (US)
Article numbere61982
JournalPloS one
Volume8
Issue number4
DOIs
StatePublished - Apr 24 2013

Fingerprint

Angiotensin Type 2 Receptor
angiotensins
hyperthyroidism
Hyperthyroidism
Vascular Smooth Muscle
blood vessels
triiodothyronine
smooth muscle
myocytes
Smooth Muscle Myocytes
Blood Vessels
Muscle
Cells
Rats
Angiotensin II Type 2 Receptor Blockers
receptors
Myosin Light Chains
Angiotensins
Renin-Angiotensin System
Phosphatidylinositol 3-Kinases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Carrillo-Sepúlveda, M. A., Ceravolo, G. S., Furstenau, C. R., de Monteiro, P. S., Bruno-Fortes, Z., Carvalho, M. H., ... Barreto-Chaves, M. L. M. (2013). Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism. PloS one, 8(4), [e61982]. https://doi.org/10.1371/journal.pone.0061982

Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism. / Carrillo-Sepúlveda, Maria Alícia; Ceravolo, Graziela S.; Furstenau, Cristina R.; de Monteiro, Priscilla Souza; Bruno-Fortes, Zuleica; Carvalho, Maria Helena; Laurindo, Francisco R.; Tostes, Rita C.; Webb, R Clinton; Barreto-Chaves, Maria Luiza M.

In: PloS one, Vol. 8, No. 4, e61982, 24.04.2013.

Research output: Contribution to journalArticle

Carrillo-Sepúlveda, MA, Ceravolo, GS, Furstenau, CR, de Monteiro, PS, Bruno-Fortes, Z, Carvalho, MH, Laurindo, FR, Tostes, RC, Webb, RC & Barreto-Chaves, MLM 2013, 'Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism', PloS one, vol. 8, no. 4, e61982. https://doi.org/10.1371/journal.pone.0061982
Carrillo-Sepúlveda MA, Ceravolo GS, Furstenau CR, de Monteiro PS, Bruno-Fortes Z, Carvalho MH et al. Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism. PloS one. 2013 Apr 24;8(4). e61982. https://doi.org/10.1371/journal.pone.0061982
Carrillo-Sepúlveda, Maria Alícia ; Ceravolo, Graziela S. ; Furstenau, Cristina R. ; de Monteiro, Priscilla Souza ; Bruno-Fortes, Zuleica ; Carvalho, Maria Helena ; Laurindo, Francisco R. ; Tostes, Rita C. ; Webb, R Clinton ; Barreto-Chaves, Maria Luiza M. / Emerging Role of Angiotensin Type 2 Receptor (AT2R)/Akt/NO Pathway in Vascular Smooth Muscle Cell in the Hyperthyroidism. In: PloS one. 2013 ; Vol. 8, No. 4.
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