NO, but not CO, attenuates anaphylaxis-induced postsinusoidal contraction and congestion in guinea pig liver

Division 2, Departments of 1 Physiology, 3 Anesthesiology, and 4 Pharmacology, Kanazawa Medical University, Uchinada 920-0293; and 2 First Department of Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan Submitted 21 October 2002 ; accepted in final form 26 September 2003 The pathophysiology of the hepatic vascular response to anaphylaxis in guinea pig is not known. We studied effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused livers derived from guinea pigs sensitized with ovalbumin. We also determined whether nitric oxide (NO) or carbon monoxide (CO) modulates the hepatic anaphylaxis. The livers were perfused portally and recirculatingly at constant flow with diluted blood. With the use of the double-occlusion technique to estimate the hepatic sinusoidal pressure (P do ), portal venous resistance (R pv ) and hepatic venous resistance (R hv ) were calculated. An antigen injection caused venoconstriction characterized by an increase in R pv greater than R hv and was accompanied by a large liver weight gain. Pretreatment with the NO synthase inhibitor N G -nitro- L -arginine methyl ester, but not the heme oxygenase inhibitor zinc protoporphyrin IX, potentiated the antigen-induced venoconstriction by increasing both R pv and R hv (2.2- and 1.2-fold increase, respectively). In conclusion, anaphylaxis causes both pre- and postsinusoidal constriction in isolated guinea pig livers. However, the increases in postsinusoidal resistance and P do cause hepatic congestion. Endogenously produced NO, but not CO, modulates these responses. hepatic circulation; antigen; double occlusion pressure; hepatic vascular resistance Address for reprint requests and other correspondence: T. Shibamoto, Dept. of Physiology, Division 2, Kanazawa Medical Univ., Uchinada 920-0293, Japan (E-mail: shibamo{at}kanazawa-med.ac.jp ).