Decreased intrahepatic response to a sub(1)-adrenergic agonists in lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function

Background and Aim: Livers from lipopolysaccharide-treated rats have a decreased vascular response to a sub(1)-adrenergic agonists due to an increased production of nitric oxide. Kupffer cells play a central role in the development of intrahepatic microvascular abnormalities during endotoxemia. We i...

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Veröffentlicht in:Journal of gastroenterology and hepatology 2007-06, Vol.22 (6), p.893-900
Hauptverfasser: Lee, Chang-Hyeong, Loureiro-Silva, Mauricio R, Abraldes, Juan G, Iwakiri, Yasuko, Haq, Omar, Groszmann, Roberto J
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Sprache:eng
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Zusammenfassung:Background and Aim: Livers from lipopolysaccharide-treated rats have a decreased vascular response to a sub(1)-adrenergic agonists due to an increased production of nitric oxide. Kupffer cells play a central role in the development of intrahepatic microvascular abnormalities during endotoxemia. We investigated the role of Kupffer cells in the intrahepatic vascular tone control in normal and endotoxemic rats. Method: Twenty-four hours after pretreatment with gadolinium chloride (to eliminateinactivate Kupffer cells) or saline, rats were treated with lipopolysaccharide or a second dose of saline. Six hours later, rats (under deep anesthesia) were submitted to liver perfusion with Krebs-Henseleit solution using a system that allowed the measurement of both perfusion and sinusoidal pressures. Dose-response curves to methoxamine (a sub(1)-adrenergic agonist) were obtained in the absence or the presence of the nitric oxide synthase inhibitor N-monomethyl-L-arginine. Results: Pretreatment with gadolinium did not change the intrahepatic vascular response to methoxamine in normal livers. Livers from lipopolysaccharide-treated rats showed a decreased sinusoidal vascular response to methoxamine and a 10-fold increase in nitric oxide production during liver perfusion. Either pretreatment with gadolinium or the presence of N-monomethyl-L-arginine in the perfusate restored the response to methoxamine and decreased the nitric oxide overproduction by more than 50%. Conclusions: Kupffer cells neither mediate nor modulate the intrahepatic vascular response to a sub(1)-adrenergic agonists in normal livers. Reduction in intrahepatic vascular response to a sub(1)-adrenergic agonists in livers from lipopolysaccharide-treated rats is located in the sinusoidal area and depends on Kupffer cell function.
ISSN:0815-9319
1440-1746
DOI:10.1111/j.1440-1746.2007.04922.x