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Decreased intrahepatic response to α 1 ‐adrenergic agonists in lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function
Author(s) -
Lee ChangHyeong,
LoureiroSilva Mauricio R,
Abraldes Juan G,
Iwakiri Yasuko,
Haq Omar,
Groszmann Roberto J
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2007.04922.x
Subject(s) - methoxamine , nitric oxide , lipopolysaccharide , endocrinology , medicine , kupffer cell , agonist , perfusion , nitric oxide synthase , receptor
Background and Aim: Livers from lipopolysaccharide‐treated rats have a decreased vascular response to α 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 eliminate/inactivate 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 (α 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 α 1 ‐adrenergic agonists in normal livers. Reduction in intrahepatic vascular response to α 1 ‐adrenergic agonists in livers from lipopolysaccharide‐treated rats is located in the sinusoidal area and depends on Kupffer cell function.