| Autor: |
Nonato AO; Institute of Biological and Health Sciences, Federal University of Mato Grosso, Av. Valdon Varjao, 6930, 78600-000, Barra do Garças, Mato Grosso, Brazil., Olivon VC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil., Dela Justina V; Institute of Biological and Health Sciences, Federal University of Mato Grosso, Av. Valdon Varjao, 6930, 78600-000, Barra do Garças, Mato Grosso, Brazil., Zanotto CZ; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil., Webb RC; Department of Physiology, Augusta University, Augusta, GA, USA., Tostes RC; Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil., Lima VV; Institute of Biological and Health Sciences, Federal University of Mato Grosso, Av. Valdon Varjao, 6930, 78600-000, Barra do Garças, Mato Grosso, Brazil., Giachini FR; Institute of Biological and Health Sciences, Federal University of Mato Grosso, Av. Valdon Varjao, 6930, 78600-000, Barra do Garças, Mato Grosso, Brazil. fernandagiachini@hotmail.com. |
| Abstrakt: |
We hypothesized that SIRS/endotoxemia-associated hyporesponsiveness to vasoconstrictors is mediated by smaller increases in intracellular Ca(2+) 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 Ca(2+); reduced contraction during Ca(2+) loading; and smaller intracellular Ca(2+) 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, Ca(2+) homeostasis is disrupted in VSMC, with decreased Ca(2+) influx, smaller concentrations of Ca(2+) in the sarcoplasmic reticulum, and decreased activation of Orai1. Abnormal Ca(2+) handling contributes to LPS-associated vascular hyporeactivity. |
Full text from SpringerLink