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

Abstract

Mice have frequently been used for a variety of physiological studies because of the development of genetic engineering. However, the characteristics of hepatic vessels such as the vascular resistance distribution and the reactivity to various vasoconstrictors are not known in mice. We therefore determined the basal levels of segmental vascular resistances and the effects of histamine and norepinephrine on the vascular resistance distribution of mice. The liver of male non-inbred ddY mice was excised and perfused via the portal vein with 5% bovine albumin-Krebs solution at a constant flow rate. The sinusoidal pressure was measured by the double occlusion pressure and used to de-The passive blood mobilization to and from the liver, which influences the venous return to the heart, is critically dependent on the location and magnitude of intrahepatic vascular resistances in relation to the compliances [1]. 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.Species differences are also found in the primary site of hepatic vasoconstriction. By using the vascular occlusion methods for measurement of the hepatic sinusoidal pressure [2, 9], we have recently shown that the hepatic longitudinal vascular responsiveness to vasoactive substances differs among different species, such as dogs, rabbits, rats, and guinea pigs [4][5][6][9][10][11]. Histamine termine the presinusoidal (R pre ) and postsinusoidal (R post ) resistances. The basal R post comprised 53 ± 1% of the total hepatic vascular resistance. The norepinephrine and histamine increased R pre in a greater magnitude than R post with liver weight loss. However, the response to histamine was weaker than that to norepinephrine. Moreover, histamine-induced vasoconstriction showed tachyphylaxis. In conclusion, the presinusoidal and postsinusoidal resistances of mouse livers were similar in magnitude. The presinusoidal vessels predominantly contract in response to norepinephrine and histamine in mouse livers. [The Japanese Journal of Physiology 55: [143][144][145][146][147][148] 2005] Key words: double occlusion pressure, isolated perfused mouse liver, sinusoidal pressure.predominantly contracts the postsinusoidal veins with resultant hepatic congestion in dogs [9, 10] and guinea pigs [11], but this substance constricts presinusoidal vessels in rabbits [4]. In rat livers, histamine did not contract or dilate hepatic vessels [11]. On the other hand, norepinephrine predominantly contracts the presinusoidal veins over the postsinusoidal veins in dogs, rabbits, rats, and guinea pigs [...

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

“…During mouse systemic anaphylaxis, PAF could be released from sensitized mast cells and macrophages (11). In addition, another anaphylactic mediator of histamine also induced liver weight loss in isolated mouse livers perfused at constant flow (24). This liver weight loss, an indicator of reduced hepatic blood volume caused by the anaphylactic mediator, suggests that this chemical mediator also acts to reduce the intrahepatic blood volume in anesthetized mice exposed to systemic anaphylaxis.…”

“…The basic method for isolated liver perfusion was described previously (24,25). The liver was perfused at a constant flow rate in a recirculating manner via the portal vein with the diluted blood.…”

“…Ppv and Phv were measured with pressure transducers connected to the corresponding sidearm with the reference point at the hepatic hilus. For measurement of double-occlusion pressure (Pdo), two solenoid valves were placed around the perfusion tubes upstream from the Ppv sidearm cannula and downstream from the Phv sidearm cannula (24). Blood flow rate (Q pv) was measured manually by collection of outflow blood for 1 min just before the baseline measurement and at the end of the experiment to confirm that blood flow was constant during the experimental period.…”

PAF, rather than Histamine, Participates in Mouse Anaphylactic Hypotension

“…We have recently demonstrated that PAF [8] and histamine [9] could constrict the hepatic vasculature in isolated perfused mouse livers. We for the first time reported that in anesthetized mice, PAF and histamine increased Ppv, which reached the maximal levels of 10-11 cm H 2 O.…”

The Sinusoidal Pressure During Ischemia-Reperfusion Injury in Perfused Mouse Liver Pretreated With or Without l-NAME

“…ac.jp. the isolated perfused mouse liver preparation in which the sinusoidal pressure can be measured with the double occlusion method [5].…”