Endothelin-1 induces direct constriction of hepatic sinusoids.
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.
Zhang
J X
JX
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
Pegoli
W
W
Clemens
M G
MG
D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction
D016232:Endothelins; D009599:Nitroprusside; D010656:Phenylephrine