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

Abstract

Ruan, Zonghai, Toshishige Shibamoto, Tomohiro Shimo, Hideaki Tsuchida, Tomonobu Koizumi, and Matomo Nishio. NO, but not CO, attenuates anaphylaxis-induced postsinusoidal contraction and congestion in guinea pig liver. Am J Physiol Regul Integr Comp Physiol 286: R94-R100, 2004. First published October 2, 2003 10.1152/ ajpregu.00648.2002The 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 (Rpv) and hepatic venous resistance (Rhv) were calculated. An antigen injection caused venoconstriction characterized by an increase in R pv greater than Rhv 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 Rhv (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 Pdo cause hepatic congestion. Endogenously produced NO, but not CO, modulates these responses. hepatic circulation; antigen; double occlusion pressure; hepatic vascular resistance ANAPHYLAXIS IS AN immediate, type-1 hypersensitivity reaction that occurs after exposure of sensitized organisms and tissues to sensitizing antigen. The most common life-threatening feature of acute anaphylaxis is cardiovascular collapse and shock, although there are other life-threatening effects, including bronchospasm, angioedema, and pulmonary edema (24). Cardiovascular manifestation includes a rapid and precipitous decrease in systemic arterial pressure with a concomitant decrease in cardiac output (5). Anaphylactic hypotension is primarily caused by alterations in the systemic circulation that influence blood flow to the heart because left ventricular function is relatively well preserved during anaphylactic shock (5). Peripheral circulatory collapse is ascribed to hypovolemia, which results from a plasma volume loss. The latter could be the result of vasodilation with the peripheral pooling in largecapacity splanchnic venous beds and increased vascular permeability with a shift of intravascular fluid to the extravascular space.In canine experimental models of anaphylactic shock, congestion of livers and the upstream splanchnic organs is important in the pathogenesis of circulatory collapse. Actually, eviscerated dogs did not develop anaphylactic shock (17). Enjeti et al. (5) reported that the severity of th...

Effects of Norepinephrine and Histamine on Vascular Resistance in Isolated Perfused Mouse Liver

“…This agrees with the study of Maass-Moreno and Rothe [13], who reported that in intact rabbit livers the pressure gradient from the hepatic sinusoids averaged 59% of the total P pv to the abdominal vena caval pressure gradient. Similar segmental vascular resistance distribution was found in guinea pig livers, in which R pre comprises 61% of R t [3,11]. The rat livers show more marked predominance of R pre over R post ; R pre is 69% of R t [11].…”

“…There are species differences in the distribution of the hepatic vascular resistance. In canine livers, the presinusoidal resistance comprises approximately 50% of the total liver vascular resistance [2], but it comprises 56% and 59% in guinea pig [3] and rabbit livers [4][5][6], respectively, and more than 60% in rat livers [7,8]. However, the basal hepatic vascular resistance distribution of mouse livers is not known, although mouse has been frequently used in physiological studies because of the development of genetic engineering.…”

Involvement of splanchnic vascular bed in anaphylactic hypotension in anesthetized BALB/c mice

“…To answer this question, we used a mouse perfused liver preparation, which provides information on changes in hepatic vascular resistance distribution and liver blood volume. However, in contrast to the sensitized perfused livers from dogs (29), rats (15,23), guinea pigs (21), and rabbits (17), hepatic anaphylactic venoconstriction did not occur in perfused mouse livers. We speculated that hepatic congestion does not occur in anesthetized sensitized mice challenged with antigen on the basis of the following findings.…”

“…Hepatic venoconstriction is observed during anaphylaxis in dogs (10), rats (15,23), guinea pigs (21), and rabbits (17). For the first time, we have demonstrated that P pv increased during systemic anaphylaxis in mice.…”

“…In addition, we recently demonstrated that the liver and splanchnic vascular beds are involved in rat anaphylactic hypotension by showing that elimination of splanchnic circulation with total hepatectomy attenuated systemic hypotension induced by the ovalbumin antigen in anesthetized sensitized rats (23). Moreover, substantial hepatic venoconstriction is also observed in anaphylaxis of rabbits (17), guinea pigs (21), cats (4), and calves (16). On the other hand, in the mouse, although immunologic mechanisms for systemic anaphylaxis have been extensively studied (11), the hemodynamic mechanism for anaphylactic shock in mice has not been well clarified because of the technical difficulty involved in measurement of hemodynamic variables in this small animal (3).…”