Endothelin-1 induces organ-specific histamine liberation and neutrophil granulocyte accumulation in the rat.
OBJECTIVE
Enhanced production of endothelin-1 (ET-1) and the activation of mast cells (MCs) have been implicated in granulocyte sequestration. We compared local consequences of transient increases in circulating ET-1 in three separate circulatory beds in pentobarbital-anesthetized Wistar rats.


METHODS
We determined whether pretreatment with ET-A receptor antagonist ETR-P1/fl peptide and MC stabilizer sodium cromoglycate would influence histamine- and granulocyte responses induced by 1 nmol/kg ET-1 iv. Plasma and tissue histamine contents were monitored, myeloperoxidase (MPO) level was determined from heart, lung and intestinal biopsies.


RESULTS
The ET-1 infusion caused significant plasma histamine elevations, enhanced MPO activity in all organs, decreased tissue histamine content in the lung and small bowel by approx. 50% , while the histamine content of heart did not change. ETR-P1/fl significantly decreased ET-1-induced intestinal and heart MPO changes, and inhibited histamine depletion in the small intestine but not in lung and heart tissues. Sodium cromoglycate inhibited the ET-1-induced neutrophil accumulation in the heart and intestine and did not influence MPO activity in the lung.


CONCLUSIONS
ET-1 release participates in the process of histamine liberation and subsequent secondary granulocyte accumulation through tissue-specific activation of ET-A receptors. ET-1-induced direct effects are predominating in pulmonary neutrophil activation, while MC-associated secondary changes play important roles in intestinal granulocyte recruitment.
Kaszaki
J
J
Institute of Surgical Research, University of Szeged, Pécsi u. 4., 6701, Szeged, Hungary. kaszaki@expsur.szote.u-szeged.hu
Czóbel
M
M
Szalay
L
L
Nagy
S
S
Boros
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D006632:Histamine