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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Nonato, Arthur Oliveira [1] ; Olivon, Vania C. [2] ; Dela Justina, Vanessa [1] ; Zanotto, Camila Z. [2] ; Clinton Webb, R. [3] ; Tostes, Rita C. [2] ; Lima, Victor V. [1] ; Giachini, Fernanda R. [1]
Total Authors: 8
Affiliation:
[1] Univ Fed Mato Grosso, Inst Biol & Hlth Sci, Av Valdon Varjao 6930, BR-78600000 Barra Do Garcas, Mato Grosso - Brazil
[2] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil
[3] Augusta Univ, Dept Physiol, Augusta, GA - USA
Total Affiliations: 3
Document type: Journal article
Source: Inflammation; v. 39, n. 3, p. 1188-1197, JUN 2016.
Web of Science Citations: 1
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. (AU)

FAPESP's process: 10/52214-6 - Contribution of oxidative stress and NOXes to diabetes-associated vascular and renal injury
Grantee:Rita de Cassia Aleixo Tostes Passaglia
Support Opportunities: Regular Research Grants