Constriction of rat extra-splenic veins to lipopolysaccharide involves endothelin-1

Naunyn Schmiedebergs Arch Pharmacol. 2010 Jun;381(6):555-62. doi: 10.1007/s00210-010-0514-9. Epub 2010 Apr 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrasentan
  • Bosentan
  • Endothelin-1 / drug effects*
  • Endothelin-1 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Hypovolemia / etiology
  • Lipopolysaccharides / toxicity*
  • Male
  • Mesentery / metabolism
  • Myography
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Endothelin A / drug effects*
  • Receptor, Endothelin A / metabolism
  • Spleen / drug effects
  • Spleen / metabolism
  • Sulfonamides / pharmacology
  • Vasoconstriction / drug effects*

Substances

  • A 192621
  • Endothelin-1
  • Lipopolysaccharides
  • Pyrrolidines
  • Receptor, Endothelin A
  • Sulfonamides
  • Bosentan
  • Atrasentan