Constriction of rat extra-splenic veins to lipopolysaccharide involves endothelin-1.
The spleen has an important role in blood volume regulation and increased resistance of post-capillary hilar veins (in mesentery adjoining the spleen) can regulate this. This study investigated whether venular constriction to lipopolysaccharide (LPS) involved endothelin-1 (ET-1). Pressure myography was used to study isolated extra-splenic (hilar) vessels from male Wistar rats (n = 111). Arteries and veins were treated with LPS (50 microg ml(-1)) for 4 h. Extra-splenic veins constricted to LPS (p < 0.05), but there was no effect on arteries. Denudation did not abolish venular constriction to LPS, indicating an endothelial independent mechanism. However, the dual ET-1 receptor antagonist bosentan (10(-5) M) and specific ET(A) and ET(B) antagonists ABT-627 (atrasentan, 6.3 x 10(-6) M) and A-192621(1.45 x 10(-6) M) completely abolished constriction of LPS-treated veins. ET-1 alone also constricted the extra-splenic arteries and veins (p < 0.05), with a greater response observed in veins (p < 0.05). ELISA also confirmed that serum and spleen levels of ET-1 increased in response to LPS (p < 0.05). That LPS-induced constriction of extra-splenic veins is mediated by ET-1. Greater constriction of post- versus pre-capillary extra-splenic vessels to LPS would result in increased intra-splenic fluid extravasation and hypovolaemia in vivo.
Mansart
Arnaud
A
Academic Unit of Anaesthesia, University of Sheffield, Royal Hallamshire Hospital, Sheffield, S10 2RX, UK.
Ruff
Lewis J
LJ
Ariaans
Mark P
MP
Ross
Jonathan J
JJ
Reilly
Charles S
CS
Brown
Nicola J
NJ
Kaufman
Susan
S
Brookes
Zoë L S
ZL
D000818:Animals; D000077868:Atrasentan; D000077300:Bosentan; D019332:Endothelin-1 / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020896:Hypovolemia / Q000209:etiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D009213:Myography; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
C120508:A 192621; D019332:Endothelin-1; D008070:Lipopolysaccharides; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D013449:Sulfonamides; D000077300:Bosentan; D000077868:Atrasentan
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