Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase

Cárnio, Evelin Capellari; Stabile, Angelita Maria; Batalhão, Marcelo Eduardo; Silva, João; Antunes‐Rodrigues, José; Branco, Luiz G.S.; Magder, Sheldon

doi:10.1007/s00424-005-1400-z

Cited by 39 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent study of our laboratory, using genetic mice lacking iNOS, showed that WT animals have a transitory increase in AVP plasma level after 2 h of LPS injection, after which its values return near basal levels. While those iNOS KO mice had higher AVP concentrations during the fourth and sixth hours when compared with WT group, which could be reflected in beneficial attenuation of hypotension (Carnio et al, 2005). Together, these data confirmed an inhibitory action of NO in AVP release.…”

Section: Discussionsupporting

confidence: 65%

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

Saia

Cárnio

2006

Life Sciences

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 65%

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

Saia

Cárnio

2006

Life Sciences

Self Cite

View full text Add to dashboard Cite

“…There were no differences between the two groups in baseline rates of apoptosis or degree of macrophage infiltration in either organ. In both the lung and the liver, LPS induced a statistically significant increase in apoptosis in both groups ( In mice, LPS-induced hemodynamic responses are regulated, in part, via the NO system (15,16). To determine if endogenous GR regulates the levels of vascular NOS, control and GR EC KO mice (n = 3 per group) were treated with vehicle or LPS (12.5 mg/kg) and aortic gene expression via qPCR was examined at 8 h post-LPS treatment.…”

Section: Loss Of Endothelial Gr Does Not Affect Apoptosis or Macrophagementioning

confidence: 99%

Endothelial glucocorticoid receptor is required for protection against sepsis

Goodwin

Feng²,

Velázquez³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

125

120

View full text Add to dashboard Cite

The glucocorticoid receptor (GR) is ubiquitously expressed on nearly all cell types, but tissue-specific deletion of this receptor can produce dramatic whole organism phenotypes. In this study we investigated the role of the endothelial GR in sepsis in vivo and in vitro. Mice with an endothelial-specific GR deletion and controls were treated with 12.5 mg/kg LPS and phenotyped. Mice lacking GR showed significantly increased mortality, more hemodynamic instability, higher nitric oxide levels, and higher levels of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) compared with controls. There were no differences in rates of apoptosis or macrophage recruitment between the two groups. Both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expression were increased after LPS challenge in mice with endothelial GR deficiency, and aminoguanidine, a specific iNOS inhibitor in mice was able to rescue hemodynamic collapse in these animals. In vitro, human umbilical vein cells (HUVECs) subjected to GR knockdown by siRNA showed increased expression of eNOS at baseline that persisted after treatment with LPS. Both eNOS and iNOS mRNA was increased by qPCR. In HUVECs lacking GR, NF-κB levels and NF-κB-dependent genes tissue factor and IL-6 were increased compared with controls. Thus, endothelial GR is a critical regulator of NF-κB activation and nitric oxide synthesis in sepsis.T he glucocorticoid receptor (GR) is a nuclear hormone receptor with wide-ranging roles in both health and disease. This receptor is a ligand-bound transcription factor that, in the absence of ligand, resides in the cytoplasm bound to Hsp90 and other stabilizing cofactors. Upon ligand binding the receptor-ligand complex translocates to the nucleus and affects gene transcription as well as a vast complement of downstream signaling pathways (1, 2). GR is the target of a number of synthetic steroids used as therapy for a wide array of autoimmune, inflammatory, and malignant conditions, as well as the receptor for the endogenous, adrenally produced steroid corticosterone.GR is present in nearly every tissue in the body and is widely conserved across species, highlighting its critical role in homeostasis and survival (3). This fact is underscored by the near uniform mortality observed in mice lacking global GR, likely due to severe lung hypoplasia (4). Thus, to address the cell-specific role of GR in mammalian systems, GR has been deleted in a tissuespecific manner. For example, deletion of GR in the central nervous system results in mice with profoundly altered hypothalamic-pituitary-adrenal (HPA) axes and 10-fold elevated circulating corticosterone levels as well as reduced anxietyrelated behavior (5). Tissue-specific excision of GR from hepatoctyes results in a severe growth deficit thought to be due to down-regulation of STAT5-mediated transcription (6, 7). Mice with tissue-specific deletion of GR in lung epithelial cells have been shown to have reduced viability (8). Therefore, the p...

show abstract

“…Elevated levels of NO may contribute to autonomic dysfunction (52) and have direct inhibitory effects on vasopressin secretion (5). Sustained elevation of hormone levels following endotoxin challenge in mice was seen in iNOS knockouts or after pharmacologic NO inhibition (53)(54)(55).…”

Section: Vasopressin In Septic Shockmentioning

confidence: 99%

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

Barrett

Singer²,

Clapp³

2007

Critical Care Medicine

199

129

View full text Add to dashboard Cite

The pathophysiologic mechanism underlying vasopressin hypersensitivity in septic shock is probably multifactorial. It is doubtful that this phenomenon is merely the consequence of replacing a deficiency. Changes in vascular receptors or their signaling and/or interactions between vasopressin, nitric oxide, and adenosine triphosphate-dependent potassium channels are likely to be relevant. Further translational research is required to improve our understanding and direct appropriate educated clinical use of vasopressin.

show abstract

Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase

Cited by 39 publications

References 30 publications

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

Endothelial glucocorticoid receptor is required for protection against sepsis

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

Contact Info

Product

Resources

About