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

3 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nonato, A. O., Olivon, V. C., Dela Justina, V., Zanotto, C. Z., Webb, R. C., Tostes, R. C., Lima, V. V., & Giachini, F. R. (2016). Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia. Inflammation, 39(3), 1188-1197. https://doi.org/10.1007/s10753-016-0354-y