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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Inflammation; v. 39, n. 3, p. 1188-1197, JUN 2016.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 10/52214-6 - Contribuição do estresse oxidativo e enzimas NADPH oxidases (NOXes) para as lesões vasculares e renais associadas ao diabetes
• Beneficiário: Rita de Cassia Aleixo Tostes Passaglia
• Modalidade de apoio: Auxílio à Pesquisa - Regular