Endothelin 1 impairs oxygen delivery in livers from LPS-primed animals.
Endothelin 1 (ET-1) is a potent vasoactive peptide that acts at sinusoidal and extrasinusoidal sites in the liver. Sensitivity to ET-1 increases in LPS-primed animals and is associated with impaired liver microcirculation in these animals. We hypothesized that LPS priming leads to an exacerbation in the impaired oxygen delivery in response to intraportal infusion of ET-1. Rats were studied 24 h after LPS injection (1 mg/kg, i.p.). Surface PO2 was determined using a recently developed technology of O2 mapping. The baseline portal pressure was higher in LPS-primed animals (P < 0.05), and increased to'similar magnitude as sham animals after a 10-min infusion of ET-1. The resultant portal pressure remained elevated in LPS compared to sham animals. There was no significant difference in baseline mean arterial pressure, and no significant systemic response to ET-1 in either group. In contrast to the macrohemodynamic, the decrease in tissue surface PO2 in response to ET-1 infusion was potentiated by LPS treatment (increased from baseline levels 33.8+/-9 to 46.8+/-8.3 in sham; 42.3+/-9.1 to 69+/-6.5 gray scale units in LPS; P < 0.01, sham vs. LPS) at end of infusion of ET-1 for 10 min. This indicates tissue hypoxia in response to ET-1, which is exacerbated in livers from LPS-primed animals compared to sham. Frequency distribution analysis showed a shift in mode from lower intensity (higher PO2) to areas with higher fluorescent intensity ranges (lower PO2), indicating areas with shut down in perfusion in LPS-treated animals. In the whole liver, ET-1 suppressed oxygen consumption, and this response was potentiated by LPS pretreatment. We propose that ET-1 impairs oxygen delivery in the liver during endotoxemia, resulting in areas of focal hypoxia. This response is possibly due to potentiated action of ET-1 at both sinusoidal and extrasinusoidal sites in the liver during endotoxemia.
Baveja
Rajiv
R
Department of Biology, University of North Carolina, Charlotte 28223, USA.
Yokoyama
Yukihiro
Y
Korneszczuk
Katarzyna
K
Zhang
Jian X
JX
Clemens
Mark G
MG
D000818:Animals; D019332:Endothelin-1 / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism*; D006439:Hemodynamics; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D008070:Lipopolysaccharides; D010100:Oxygen