PMID- 22994521
OWN - NLM
STAT- MEDLINE
DCOM- 20130320
LR  - 20211021
IS  - 1557-8682 (Electronic)
IS  - 1527-0297 (Print)
IS  - 1527-0297 (Linking)
VI  - 13
IP  - 3
DP  - 2012 Sep
TI  - Effect of endothelin receptor antagonist bosentan on chronic hypoxia-induced 
      inflammation and chemoafferent neuron adaptation in rat carotid body.
PG  - 209-16
AB  - Chronic hypoxia (CH) induces an inflammatory response in rat carotid body that is 
      characterized by immune cell invasion and the expression of pro-inflammatory 
      cytokines. In the present study, we have investigated the role of type-A 
      endothelin (ET-A) receptors in the development of CH-induced inflammation. After 
      7 days of CH (380 Torr), double-label immunofluorescence studies demonstrated 
      elevated levels of ET-A receptor and tyrosine hydroxylase (TH) in O(2)-sensitive 
      type I cells. Following CH, ET-A receptors were also expressed on resident and 
      invasive CD45+ immune cells distributed in tissue surrounding chemosensory cell 
      lobules. Immnofluorescence and quantitative PCR studies showed that concurrent 
      treatment with the ET-A/B receptor antagonist, bosentan (200 mg/kg/day), blocked 
      CH-induced ED-1+ macrophage invasion and the upregulation of cytokines, including 
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and 
      monocyte chemoattractant protein-1 (MCP-1). Moreover, bosentan treatment blocked 
      the CH-induced increases in expression of acid-sensitive ion channels (ASICs) in 
      chemoafferent neurons in the petrosal ganglion (PG). Our findings are consistent 
      with the hypothesis that CH-induced inflammation involves the upregulation and 
      release of ET-1 from type I cells. ET-1 may act in an autocrine/paracrine 
      mechanism via ET-A receptors on chemosensory type I cells and immune cells to 
      promote an inflammatory response.
FAU - Liu, Xuemei
AU  - Liu X
AD  - Department of Physiology, University of Utah School of Medicine, Salt Lake City, 
      Utah 84108, USA.
FAU - He, Liang
AU  - He L
FAU - Dinger, Bruce
AU  - Dinger B
FAU - Stensaas, Larry
AU  - Stensaas L
FAU - Fidone, Salvatore
AU  - Fidone S
LA  - eng
GR  - HL-086508/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - High Alt Med Biol
JT  - High altitude medicine & biology
JID - 100901183
RN  - 0 (Acid Sensing Ion Channels)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endothelin-1)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Receptor, Endothelin A)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Acid Sensing Ion Channels/drug effects
MH  - Adaptation, Physiological/drug effects
MH  - Animals
MH  - Antihypertensive Agents/pharmacology/*therapeutic use
MH  - Bosentan
MH  - Carotid Body/immunology
MH  - Cell Movement/drug effects
MH  - Chemokine CCL2/genetics/metabolism
MH  - Chemoreceptor Cells/drug effects/*physiology
MH  - Chronic Disease
MH  - Endothelin-1/metabolism
MH  - Gene Expression/drug effects
MH  - Hypoxia/complications/*metabolism
MH  - Inflammation/*drug therapy/etiology/*metabolism
MH  - Interleukin-1/genetics/metabolism
MH  - Interleukin-1beta/genetics/metabolism
MH  - Leukocyte Common Antigens/metabolism
MH  - Macrophages/drug effects
MH  - Rats
MH  - Receptor, Endothelin A/metabolism
MH  - Sulfonamides/pharmacology/*therapeutic use
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
PMC - PMC3448101
EDAT- 2012/09/22 06:00
MHDA- 2013/03/21 06:00
PMCR- 2013/09/01
CRDT- 2012/09/22 06:00
PHST- 2012/09/22 06:00 [entrez]
PHST- 2012/09/22 06:00 [pubmed]
PHST- 2013/03/21 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1089/ham.2012.1011 [pii]
AID - 10.1089/ham.2012.1011 [doi]
PST - ppublish
SO  - High Alt Med Biol. 2012 Sep;13(3):209-16. doi: 10.1089/ham.2012.1011.