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 language | English (US) |
|---|---|
| Pages (from-to) | 1188-1197 |
| Number of pages | 10 |
| Journal | Inflammation |
| Volume | 39 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 1 2016 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia
AU - Nonato, Arthur Oliveira
AU - Olivon, Vania C.
AU - Dela Justina, Vanessa
AU - Zanotto, Camila Z.
AU - Webb, R Clinton
AU - Tostes, Rita C.
AU - Lima, Victor V.
AU - Giachini, Fernanda R.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - calcium homeostasis
KW - hypotension
KW - vascular reactivity
KW - vascular smooth muscle cell
UR - http://www.scopus.com/inward/record.url?scp=84964319083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964319083&partnerID=8YFLogxK
U2 - 10.1007/s10753-016-0354-y
DO - 10.1007/s10753-016-0354-y
M3 - Article
C2 - 27099074
AN - SCOPUS:84964319083
VL - 39
SP - 1188
EP - 1197
JO - Inflammation
JF - Inflammation
SN - 0360-3997
IS - 3
ER -