Endothelin-1 induces direct constriction of hepatic sinusoids

Am J Physiol. 1994 Apr;266(4 Pt 1):G624-32. doi: 10.1152/ajpgi.1994.266.4.G624.


We studied the hepatic microvascular response to endothelin (ET) and the possible role of Ito cells (fat-storing cells) acting as pericytes in this response using isolated rat livers under high-power intravital microscopy. Livers were perfused in a modified pressure-controlled system with Krebs buffer plus rat erythrocytes (RBC, 10%), and sinusoids at the site of Ito cells were observed under a x 100 objective (total magnification x 2,533) before and during infusion of ET-1 (10(-9 M) alone, sodium nitroprusside (NP, 10(-5) M). plus ET-1, or phenylephrine (PE, 10(-7) M). Both ET-1 and PE decreased portal flow (25 and 51%) and increased inflow pressure (28 and 43%), respectively. PE had no effect on any sinusoidal parameters except that it decreased measured sinusoidal RBC velocity (P < 0.05); ET-1 decreased sinusoidal diameter by 25% and increased the calculated sinusoidal pressure gradient and resistance by 116 and 350%, respectively, but did not alter RBC velocity. NP significantly inhibited changes induced by ET-1. These results demonstrate that ET-1 induces a specific sinusoidal constriction that disrupts normal acinar flow dynamics, and the sinusoidal constriction colocalizes with Ito cells, suggesting that the constriction may be mediated at least in part by ET-1 action on Ito cells, which can be inhibited by a nitric oxide donor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endothelins / pharmacology*
  • Hemodynamics / drug effects
  • Humans
  • Liver Circulation / drug effects*
  • Liver Circulation / physiology
  • Male
  • Nitroprusside / pharmacology
  • Phenylephrine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Vasoconstriction*


  • Endothelins
  • Nitroprusside
  • Phenylephrine