Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia

Arthur Oliveira Nonato, Vania C. Olivon, Vanessa Dela Justina, Camila Z. Zanotto, R Clinton Webb, Rita C. Tostes, Victor V. Lima, Fernanda R. Giachini

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We hypothesized that SIRS/endotoxemia-associated hyporesponsiveness to vasoconstrictors is mediated by smaller increases in intracellular Ca2+ levels due to reduced signaling via the STIM/Orai. Male Wistar rats were injected either with saline or bacterial LPS (i.p.; 10 mg/kg), and experiments were performed 24 h later. LPS-injected rats exhibited decreased systolic blood pressure, increased heart rate, neutrophils’ migration into the peritoneal cavity, and elevated alanine aminotransferase levels. Additionally, second-order mesenteric arteries from endotoxemic rats displayed hyporeactivity to contractile agents such as phenylephrine and potassium chloride; decreased contractile responses to Ca2+; reduced contraction during Ca2+ loading; and smaller intracellular Ca2+ stores. Decreased Orai1, but not STIM1, expression was found in resistance mesenteric arteries from LPS-treated rats. Additionally, cultured vascular smooth muscle cell (VSMC) treated with LPS resulted in increased TLR-4 expression, but Myd-88 and STIM-1 expression were not changed. Our data suggest that in endotoxemia, Ca2+ homeostasis is disrupted in VSMC, with decreased Ca2+ influx, smaller concentrations of Ca2+ in the sarcoplasmic reticulum, and decreased activation of Orai1. Abnormal Ca2+ handling contributes to LPS-associated vascular hyporeactivity.

Original languageEnglish (US)
Pages (from-to)1188-1197
Number of pages10
JournalInflammation
Volume39
Issue number3
DOIs
StatePublished - Jun 1 2016

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Endotoxemia
Vasoconstrictor Agents
Homeostasis
Mesenteric Arteries
Vascular Smooth Muscle
Smooth Muscle Myocytes
Blood Pressure
Potassium Chloride
Peritoneal Cavity
Sarcoplasmic Reticulum
Phenylephrine
Alanine Transaminase
Blood Vessels
Wistar Rats
Neutrophils
Heart Rate

Keywords

  • calcium homeostasis
  • hypotension
  • vascular reactivity
  • vascular smooth muscle cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia. / Nonato, Arthur Oliveira; Olivon, Vania C.; Dela Justina, Vanessa; Zanotto, Camila Z.; Webb, R Clinton; Tostes, Rita C.; Lima, Victor V.; Giachini, Fernanda R.

In: Inflammation, Vol. 39, No. 3, 01.06.2016, p. 1188-1197.

Research output: Contribution to journalArticle

Nonato, AO, Olivon, VC, Dela Justina, V, Zanotto, CZ, Webb, RC, Tostes, RC, Lima, VV & Giachini, FR 2016, 'Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia', Inflammation, vol. 39, no. 3, pp. 1188-1197. https://doi.org/10.1007/s10753-016-0354-y
Nonato, Arthur Oliveira ; Olivon, Vania C. ; Dela Justina, Vanessa ; Zanotto, Camila Z. ; Webb, R Clinton ; Tostes, Rita C. ; Lima, Victor V. ; Giachini, Fernanda R. / Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia. In: Inflammation. 2016 ; Vol. 39, No. 3. pp. 1188-1197.
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