Vessel- and target cell-specific actions of endothelin-1 and endothelin-3 in rat liver.
We studied the sinusoidal and extrasinusoidal constrictor response of hepatic microcirculation to endothelin-1 (ET-1) and endothelin-3 (ET-3) and the possible role of Ito cells vs. Kupffer cells or endothelial cells in mediating this response, using isolated rat livers under high-power intravital microscopy. Rats were pretreated by injection of 2.6 x 10(8) fluorescent latex beads (1 micron) intravenously to label Kupffer cells. Three hours later livers were isolated and perfused before and during the infusion of 1 nM ET-1 or ET-3 with or without the endothelin type A (ETA) receptor antagonist BQ-123 or ETB antagonist IRL-1038. Alternatively, the perfused livers were infused with the ETB agonist sarafotoxin 6c (S6c, 1 or 5 nM). Sinusoid diameters were quantitated at the sites of Ito cells (identified by vitamin A fluorescence) or Kupffer cells (phagocytosed fluorescent latex beads) or where neither cell type was found (endothelial cells). ET-1 was found to induce significant sinusoid constriction at the sites of Ito cells (13.21 +/- 0.58 microns control vs. 10.47 +/- 0.48 microns during ET-1 infusion) but not at the sites of Kupffer cells or endothelial cells (13.26 +/- 0.79 vs. 12.92 +/- 0.61 microns and 12.20 +/- 0.71 vs. 11.98 +/- 0.40 microns, respectively), whereas neither ET-3 nor S6c had any effect on sinusoid narrowing, despite a 1.8-fold (ET-3) or 5.6-fold (5 nM S6c) greater increase in total portal resistance compared with ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhang
J X
JX
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Bauer
M
M
Clemens
M G
MG
D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007728:Kupffer Cells / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D011168:Portal System / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000502:physiology; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D010456:Peptides, Cyclic; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu)