Hypophysial portal blood flow during preganglionic stimulation of the superior cervical ganglion under condition of systemic arterial blood pressure stabilization in rat.

The presence of hypothalamic hormones in the pituitary portal blood is regarded as the principal factor by which the hypothalamus controls pituitary secretion. In contrast to numerous investigations on hypothalamic hormone release, the regulation of the hypophysial-portal blood flow (HPBF) has been scarcely studied. Hypophysial-portal vessels were exposed according to the Worthington's method [1966]. The 10-min blood samples were collected before and during unilateral or alternative bilateral electrical stimulation of the preganglionic fibers of the superior cervical ganglia (SCG). During blood samples collection the stable systemic arterial blood pressure was maintained by a barostat. The HPBF was estimated according to the determination of the hemoglobin in samples of washed and collected blood from the cut pituitary portal vessels. The mean HPBF was 3.5 microliters/min. Electrical stimulation of SCG. did not change HPBF. This indicates that sympathetic efferents do not participate in the regulation of HPBF under conditions of stabilization of the systemic arterial blood pressure.     

Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements

Intrahepatic pressure (9.4 +/- 0.3 mmHg; 1 mmHg = 133.32 Pa), measured proximal to a hepatic venous resistance site, was insignificantly different from portal venous pressure (9.6 +/- 0.4 mmHg). This lobar venous pressure is not wedged hepatic venous pressure as it is measured from side holes in a catheter with a sealed tip. Validation of the lobar venous pressure measurement was done in a variety of ways and using different sizes and configurations of catheters. The site of hepatic venous resistance in the dog is localized to a narrow sphincterlike region about 0.5 cm in length and within 1-2 cm (usually within 1 cm) of the junction of the vena cava and hepatic veins. Sinusoidal and portal venous resistance appears insignificant in the basal state and large increases in liver blood volume (histamine infusion or passive vena caval occlusion) or large decreases in liver blood volume (passive vascular occlusion) do not alter the insignificant pressure gradient between portal and lobar venous pressures. Norepinephrine infusion (1.25 microgram X kg-1 X min-1 intraportal) and hepatic sympathetic nerve stimulation (10 Hz) led to a significantly greater rise in portal venous pressure than in lobar venous pressure, indicating some presinusoidal (and (or) sinusoidal) constriction and this indicates that lobar venous pressure cannot be assumed under all conditions to accurately reflect portal pressure. However, most of the rise in portal venous pressure induced by intraportal infusion of norepinephrine or nerve stimulation and virtually all of the pressure rise induced by histamine could be attributed to the postsinusoidal resistance site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of reinfusions of autologous blood on the systemic and portal circulation in acute blood loss in rats

The experiments on rats using the method of contact luminescent biomicroscopy coupled with the ultrasonic measurement of systemic blood pressure and blood flow velocity in the portal vein and hepatic artery have revealed that portal micro- and macrocirculation reflects the degree of efficacy of acute hemorrhage treatment with autoblood. Autoblood infusion in animals with compensatory type of posthemorrhagic period restored systemic blood pressure and blood flow velocity in the portal vein and hepatic artery, promoting the development of erythrocyte aggregation and local microcirculation disturbances in the central zone of hepatic functional elements.     

Effects of Hct and norepinephrine on segmental vascular resistance distribution in isolated perfused rat livers

We studied the effects of blood hematocrit (Hct), blood flow, or norepinephrine on segmental vascular resistances in isolated portally perfused rat livers. Total portal hepatic venous resistance (Rt) was assigned to the portal (Rpv), sinusoidal (Rsinus), and hepatic venous (Rhv) resistances using the portal occlusion (Ppo) and the hepatic venous occlusion (Phvo) pressures that were obtained during occlusion of the respective line. Four levels of Hct (30%, 20%, 10%, and 0%) were studied. Rpv comprises 44% of Rt, 37% of Rsinus, and 19% of Rhv in livers perfused at 30% Hct and portal venous pressure of 9.1 cmH2O. As Hct increased at a given blood flow, all three segmental vascular resistances of Rpv, Rsinus, and Rhv increased at flow >15 ml/min. As blood flow increased at a given Hct, only Rsinus increased without changes in Rpv or Rhv. Norepinephrine increased predominantly Rpv, and, to a smaller extent, Rsinus, but it did not affect Rhv. Finally, we estimated Ppo and Phvo from the double occlusion maneuver, which occluded simultaneously both the portal and hepatic venous lines. The regression line analysis revealed that Ppo and Phvo were identical with those measured by double occlusion. In conclusion, changes in blood Hct affect all three segmental vascular resistances, whereas changes in blood flow affect Rsinus, but not Rpv or Rhv. Norepinephrine increases mainly presinusoidal resistance. Ppo and Phvo can be obtained by the double occlusion method in isolated perfused rat livers.     

Adenosine modulation of hepatic arterial but not portal venous constriction induced by sympathetic nerves, norepinephrine, angiotensin, and vasopressin in the cat

Intrinsic regulation of hepatic arterial blood flow depends upon local concentrations of adenosine. The present data show that i.a. infusions of adenosine cause dilation of the hepatic artery and inhibition of arterial vasoconstriction induced by norepinephrine, vasopressin, angiotensin, and hepatic nerve stimulation. Vasoconstriction induced by submaximal nerve stimulation (2 Hz) and norepinephrine infusions (0.25 and 0.5 micrograms X kg-1 X min-1, i.p.v.) were equally inhibited by adenosine. Supramaximal nerve stimulation (8 Hz) was inhibited to a lesser extent. The data are consistent with the hypotheses that (a) adenosine causes nonselective inhibition of vasoconstrictor influences on the hepatic artery; and (b) adenosine antagonizes neurally induced vasoconstriction by a purely postsynaptic effect and does not decrease norepinephrine release. In contrast with the hepatic artery, the intrahepatic portal resistance vessels are not affected by even large doses of adenosine; neither responses in basal tone nor antagonism of vasoconstrictor effects of nerve stimulation, norepinephrine, or angiotensin could be demonstrated. The data are consistent with the hypothesis that the smooth muscle of the portal resistance vessels does not contain adenosine receptors, whereas adenosine receptors on the smooth muscle of the hepatic arterial resistance vessels are of major regulatory importance. Whether endogenous levels of adenosine can reach sufficient concentration to modulate endogenous constrictors remains to be determined.     

Hepatic Arterial Vasodilation Is Independent of Portal Hypertension in Early Stages of Cirrhosis

Introduction

The compensatory increase in hepatic arterial flow with a decrease in portal venous flow is known as the hepatic arterial buffer response. In cirrhosis with elevated portal pressure, the vascular resistance of the hepatic artery is decreased. Whether this lower resistance of the hepatic artery is a consequence of portal hypertension or not remains unknown.

Study Aim

The aim of the study was to investigate the hepatic arterial resistance and response to vasoconstriction in cirrhosis without portal hypertension (normal portal resistance).

Methods

Cirrhosis was induced by CCl₄-inhalation for 8 weeks (8W, normal portal resistance) and for 12–14 weeks (12W, elevated portal resistance). Bivascular liver perfusion was performed at 8W or 12W and dose response curves of methoxamine were obtained in the presence or absence of LNMMA (nitric oxide synthase blocker). Vascular resistances of the hepatic artery (HAR), portal vein (PVR) and sinusoids (SVR) were measured. Western Blot (WB) and Immunohistochemistry (IHC) were done to measure eNOS and HIF 1a expression.

Results

HAR in both groups of cirrhotic animals (8W and 12W) were lower compared to controls. Dose response curves to methoxamine revealed lower HAR in both cirrhotic models (8W and 12W) regardless the magnitude of portal resistance. LNMMA corrected the dose response curves in cirrhosis (8W and 12W) to control. WB and IHC show increased protein expression of eNOS and HIF1a in 8W and 12W.

Conclusion

Hepatic arterial resistance is decreased in cirrhosis independent of portal resistance. Vasodilation of the hepatic artery in cirrhosis seems to be influenced by hypoxia rather than increase in portal resistance. Nitric oxide is the main vasodilator.     

Combined Hepatic Vein, Umbilicoportal Vein, and Superior Mesenteric Artery Catheterization in Portal Hypertension: Estimation of the Portal Fraction of Total Hepatic Blood Flow in Cirrhotic Patients

Hemodynamic data were obtained in 13 cirrhotic patients with severe portal hypertension, undergoing combined hepatic vein, umbilicoportal vein, and superior mesenteric artery catheterization. The relative clearance of indocyanine green, the portohepatic gradient (difference between the free portal venous pressure and the free hepatic venous pressure), and the estimated hepatic blood flow were measured. The portal fraction (PF) of total hepatic blood flow was calculated in all patients using indicator dilution curves obtained from the portal bifurcation, a right hepatic vein, and when possible a left hepatic vein (six cases) after injection of ⁵¹Cr-labeled red blood cells (⁵¹Cr RBC) into the superior mesenteric artery. Flows were overestimated because of loss of indicator through spontaneous portosystemic shunts; however, the ratio between hepatic and portal indicator dilution curves can be used to calculate the portal fraction of total hepatic blood flow since no extrahepatic shunts existed after the bifurcation of the portal vein (as shown on portography). In 10 patients, 15 series of curves were calculable and the PF varied between 30.1 and 100% (mean ± SE: 71.1 ± 6.2%). In the three other patients, only delayed activity from recirculation was detected from portal and hepatic vein samples and PF was 0%; in these three cases, portography and arteriography revealed spontaneous portacaval shunting with reverse and/or stagnant circulation in the portal vein. In the 13 patients, no correlation existed between PF and the relative clearance of indocyanine green or the portohepatic gradient, parameters generally used as indices of severity in cirrhosis. In 10 patients, no correlation was found between PF and the estimated hepatic blood flow.     

Effects of endothelin and vasopressin on portal pressure of rats

Endothelin is a vasoconstrictor peptide which has recently been isolated and sequenced from the vascular endothelial cells. It was reported to increase blood pressure in vivo and produce a prolonged contraction with a slow onset in vitro. The purpose of this study was to investigate whether endothelin can lower the portal pressure as another endogenous vasoconstriction peptidevasopressin (AVP) can. Heart rate, systemic blood pressure, portal pressure, and portal vein blood flow were measured. Effects of endothelin on these parameters were compared with those of AVP. Endothelin 10(-10) mol/Kg significantly decreased all of the parameters mentioned. At the higher dose (5 x 10(-10) mol/Kg), however, the portal pressure and blood pressure were increased and portal vein blood flow was unchanged. On the other hand, AVP decreased the portal pressure and portal vein blood flow but elevated the systemic blood pressure. In vitro experiments revealed that endothelin contracted both tail artery and portal vein of rat and vasopressin contracted only tail artery. We concluded that although both are endogenous vasoconstricting peptides, endothelin and AVP affect differently on arterial and venous vascular beds as well as on portal pressure.     

Hemodynamic effects of Salvia miltiorrhiza on cirrhotic rats

Salvia miltiorrhiza (Sm) administration has been shown to reduce hepatic fibrosis in rats. We investigated the hemodynamic effects of Sm on bile duct ligated (BDL) rats. Hemodynamic, histological, and vascular contractile studies were conducted in rats 4 weeks after bile duct ligation. An aqueous extract of Sm (0.2 g twice per day) or vehicle was administered for 4 weeks to BDL rats. Sm treatment in BDL rats significantly reduced histological grades of fibrosis and ameliorated the portal hypertensive state (including portal venous pressure, superior mesenteric artery blood flow, cardiac index, and total peripheral resistance) as compared with vehicle treatment. Moreover, Sm treatment enhanced the vascular sensitivity of mesenteric arteries to phenylephrine in BDL rats. Sm treatment had no effect on plasma biochemical profiles of either BDL or normal rats. Our results suggest that 4-week Sm treatment ameliorates the portal hypertensive state in BDL rats.     

The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery

Reduction of portal blood flow results in compensatory vasodilation of the hepatic artery, the hepatic arterial buffer response. The hypothesis tested is that the regulation of the buffer response is mediated by adenosine, where the local concentration of adenosine in the region of the hepatic arterial resistance vessels is regulated by washout of adenosine into portal venules that are in intimate contact with hepatic arterioles. In anesthetized cats, portal flow was reduced to zero by complete occlusion of all arterial supply to the guts. The resultant dilation of the hepatic artery compensated for 23.9 +/- 4.9% of the decrease in portal flow. Dose-response curves were obtained for the effect of intraportal adenosine infusion on hepatic arterial conductance in doses that did not lead to recirculation and secondary effects on the hepatic artery via altered portal blood flow. The dose to produce one-half maximal response for adenosine is 0.19 mg X kg-1 X min-1 (intraportal) and the estimated maximal dilation is equivalent to an increase in hepatic arterial conductance to 245% of the basal (100%) level. The adenosine antagonist, 8-phenyltheophylline, produced dose-related competitive antagonism of the dilator response to infused adenosine (but not to isoproterenol) and a similar, parallel antagonism of the hepatic arterial buffer response. If supramaximal blocking doses were used, the hepatic artery showed massive and prolonged constriction with blood flow decreasing to zero. The data strongly support the hypothesis that intrinsic hepatic arterial buffer response is mediated entirely by local adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response.

Intrahepatic arteries are richly innervated by both adrenergic and sensory vanilloid-sensitive (capsaicin-sensitive) fibers. Stimulation of capsaicin sensitive fibers has been shown to dilate the intrahepatic vessels by both releasing sensory neuropeptides and by modulating the adrenergic tone. However the participation of capsaicin-sensitive fibers in the mediation of the hepatic artery buffer response (HABR) has not been investigated yet. To explore the involvement of sensory innervation and sensory neuropeptides in the HABR, the experiments were performed on capsaicin-denervated Wistar rats. In addition, we used selective CGRP and tachykinin receptor antagonists to test the participation of CGRP, substance P and NK-A in HABR in the rat. In anesthetized rats the hepatic artery blood flow (HABF), microcirculatory hepatic blood flow (HBF) and portal blood flow (PBF) were determined. The HABR was induced by partial occlusion of the portal vein and maintaining the PBF at 10% of its control preocclusive value. In the control HABR the hepatic artery blood flow increased by 89% (p< 0.005) whilst the HBF at the same time decreased by 32% (p< 0.005) in comparison to preocclusive HABF and HBF values. In sensory-denervated rats the resting HBF and PBF were increased by 23% (p< 0.05) and 34% (p< 0.05), respectively in comparison to the control HBF and PBF values. In this group the induction of the HABR increased the hepatic artery blood flow by only 55% (p< 0.05), whilst the HBF was reduced by 45% (p< 0.05). Pretreatment with CGRP 8-37 (CGRP receptor antagonist) and NK-1 but not NK-2 nor NK-3 receptor antagonists significantly reduced the HABF by 43% (p< 0.05) and 25% (p< 0.05) as compared to the HABF value in the control HABR group. These findings support the hypothesis that the hepatic artery buffer response induced by reduction of the portal inflow to the liver by 90% is partially mediated by activation of capsaicin-sensitive sensory fibers in the liver, probably due to local tissue ischemia and hypoxia. The observed vasodilation in the vascular bed of the hepatic artery is due to stimulation of CGRP and NK-1 receptors.     

Hepatic neovascularization after partial portal vein ligation: novel mechanism of chronic regulation of blood flow

The present study was undertaken to investigate hepatic microcirculatory response following partial portal vein ligation (PPVL) in rats. Portal pressure was markedly increased 2-6 wk after PPVL, but no significant reduction in sinusoidal perfusion and hepatocellular injury were detected. However, marked neovascularization was observed in PPVL rats using intravital microscopy and scanning electron microscopy (SEM). Extremely high red blood cell velocity (2,000-4,900 microm/s) was seen in these vessels. Injection of fluorescein sodium via the carotid artery revealed that the neovessels originated from the hepatic arterial vasculature. This was further confirmed by clamping the common hepatic artery and phenylephrine injection from the carotid artery. These vessels maintained sufficient flow after massive sinusoidal shutdown elicited by the portal infusion of endothelin receptor B agonist IRL-1620. SEM also showed extensive neovascularization at the hilum. Additionally, clamping the portal vein decreased sinusoidal perfusion only by 9.5% in PPVL, whereas a 71.2% decrease was observed in sham. These results strongly suggest that the liver maintains its microcirculatory flow by vascular remodeling from the hepatic arterial vasculature following PPVL.     

Effect of hepatic venous sphincter contraction on transmission of central venous pressure to lobar and portal pressure

In dogs anesthetized with pentobarbital, central vena caval pressure (CVP), portal venous pressure (PVP), and intrahepatic lobar venous pressure (proximal to the hepatic venous sphincters) were measured. The objective was to determine some characteristics of the intrahepatic vascular resistance sites (proximal and distal to the hepatic venous sphincters) including testing predictions made using a recent mathematical model of distensible hepatic venous resistance. The stimulus used was a brief rise in CVP produced by transient occlusion of the thoracic vena cava in control state and when vascular resistance was elevated by infusions of norepinephrine or histamine, or by nerve stimulation. The percent transmission of the downstream pressure rise to upstream sites past areas of vascular resistance was elevated. Even small increments in CVP are partially transmitted upstream. The data are incompatible with the vascular waterfall phenomenon which predicts that venous pressure increments are not transmitted upstream until a critical pressure is overcome and then further increments would be 100% transmitted. The hepatic sphincters show the following characteristics. First, small rises in CVP are transmitted less than large elevations; as the CVP rises, the sphincters passively distend and allow a greater percent transmission upstream, thus a large rise in CVP is more fully transmitted than a small rise in CVP. Second, the amount of pressure transmission upstream is determined by the vascular resistance across which the pressure is transmitted. As nerves, norepinephrine, or histamine cause the hepatic sphincters to contract, the percent transmission becomes less and the distensibility of the sphincters is reduced. Similar characteristics are shown for the "presinusoidal" vascular resistance and the hepatic venous sphincter resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diminished hyperaemic response of the hepatic artery to portal venous occlusion (the buffer response) in Asian hybrid minipigs: a comparison of the response to that observed in dogs

The hyperaemic response of the hepatic artery to portal vein occlusion (the buffer response) and the action of exogenous adenosine upon hepatic artery blood flow was studied in Asian hybrid minipigs as a potential alternative experimental model to that previously developed in dogs. Adenosine produced a dose-dependent hepatic artery vasodilatation, but of lesser extent than that observed in dogs. A greatly diminished buffer response was observed in the pigs compared to that seen in dogs, and could not be replicated consistently. The adenosine uptake inhibitor dipyridamole did not potentiate responses to adenosine or the buffer response. It is concluded that the minipig is an unsuitable alternative model for the study of the hepatic artery buffer response.Abbreviations bw body weight - DPD dipyridamole - GDV gastroduodenal vein - HA hepatic artery - PV portal vein - PVO portal venous occlusion - PVP portal venous pressure - SE standard error     

Presinusoidal vessels predominantly contract in response to norepinephrine, histamine, and KCl in rabbit liver.

In rabbit livers, it is not well known which segments of the hepatic vasculature are predominantly contracted by various vasoconstrictors. We determined effects of histamine, norepinephrine, and KCl on hepatic vascular resistance distribution in isolated rabbit livers perfused via the portal vein with 5% albumin-Krebs solution at a constant flow rate. Hepatic capillary pressure was measured by double vascular occlusion pressure (Pdo) and was used to determine portal (Rpv) and hepatic venous (Rhv) resistances. A bolus injection of either histamine or norepinephrine dose-dependently increased portal venous pressure but not Pdo, resulting in a dose-dependent increase in Rpv and no changes in Rhv. KCl (50 mM), when injected in anterogradely perfused livers, contracted the presinusoidal vessels selectively with liver weight loss. Although KCl significantly increased Rhv in retrogradely perfused livers, the increase in Rpv by 400% of baseline predominated over the increase in Rhv by 85% of baseline. In the retrogradely perfused livers, KCl produced an initial liver weight loss followed by a profound weight gain. We conclude that histamine and norepinephrine selectively contract the presinusoidal vessels. The results on KCl effects suggest that this selective presinusoidal constriction might be possibly due to predominant distribution of functionally active vascular smooth muscle in the presinusoidal vessels rather than the hepatic vein in rabbit livers.     

Differentiated interaction of hypothalamic and bulbar mechanisms in regulating blood flow in skeletal muscles

Acute experiments on dogs anesthetized with chloralose and numbutal were made to examine the changes in the blood flow in the muscles of hind limbs in response to stimulation of different parts of the hypothalamus before and after elimination of the effects of the main reflexogenic zones. Vasodilatation in leg muscles evoked by stimulation of the anterior hypothalamus (supraoptic dorso- and ventro-medial nuclei) increased after elimination of baroceptor effects. Qualitatively, the same response evoked by stimulation of the mamillary nuclei diminished. A conclusion has been made about differential interaction of the hypothalamic and bulbar mechanisms in muscle circulation control. It is assumed that vasodilatation of the skeletal muscles evoked by stimulation of the posterior hypothalamus might be determined by reflex inhibition of the vascular tone.     

Glucose-dependent insulinotropic peptide: differential effects on hepatic artery vs. portal vein endothelial cells

Glucose-dependent insulinotropic peptide (GIP) has been reported to have opposing effects on splanchnic blood flow. GIP infusion in dogs results in an increase in portal vein circulation but a drop in hepatic artery blood flow. In an effort to evaluate whether these different responses were related to intrinsic differences in GIP effects, we isolated canine hepatic artery (HAEC) and portal vein endothelial cells (PVEC). We report that there are differences in GIP activation of the signal transduction pathways in these two cell types. GIP stimulates secretion of endothelin-1 (ET-1), a potent vasoconstrictor, from HAEC (EC50 0.28 nM) but not from PVEC. This effect could be abolished by preventing a rise in intracellular calcium, demonstrating the calcium dependence of GIP-induced ET-1 secretion from HAEC. The GIP effect was specific, as a GIP receptor antagonist blocked it. In contrast, GIP stimulated nitric oxide production from PVEC (EC50 0.09 nM) but not from HAEC. Taken together, our data demonstrate distinct differences in GIP effects on HAEC from those on PVEC. We conclude that differences in GIP stimulation of ET-1 vs. nitric oxide production in different vascular beds may account for some of the observed differences in its physiological effects.     

Differential responses of regional sympathetic activity and blood flow to visceral afferent stimulation

The sympathetic nervous system is essential for the cardiovascular responses to stimulation of visceral afferents. It remains unclear how the reflex-evoked sympathetic output is distributed to different vascular beds to initiate the hemodynamic changes. In the present study, we examined changes in regional sympathetic nerve activity and blood flows in anesthetized cats. Cardiovascular reflexes were induced by either electrical stimulation of the right splanchnic nerve or application of 10 microg/ml of bradykinin to the gallbladder. Blood flows were measured using colored microspheres or the Transonic flow meter system. Sympathetic efferent activity was recorded from the left splanchnic, inferior cardiac, and tibial nerves. Stimulation of visceral afferents decreased significantly blood flows in the celiac (from 49 +/- 4 to 25 +/- 3 ml/min) and superior mesenteric (from 35 +/- 4 to 23 +/- 2 ml/min) arteries, and the vascular resistance in the splanchnic bed was profoundly increased. Consistently, stimulation of visceral afferents decreased tissue blood flows in the splanchnic organs. By contrast, activation of visceral afferents increased significantly blood flows in the coronary artery and portal vein but did not alter the vascular resistance of the femoral artery. Furthermore, stimulation of visceral afferents increased significantly sympathetic efferent activity in the splanchnic (182 +/- 44%) but not in the inferior cardiac and tibial nerves. Therefore, this study provides substantial new evidence that stimulation of abdominal visceral afferents differentially induces sympathetic outflow to the splanchnic vascular bed.     

Effects of ventromedial and lateral hypothalamic stimulation on chemically-induced liver injury in rats

The effects of hypothalamic stimulation on experimental liver injury induced by carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN) were studied in rats, by measuring plasma alanine aminotransferase (ALT) activity as an index of acute liver injury. Electrical stimulation of the ventromedial hypothalamus (VMH) in CCl4-treated rats caused a marked increase in plasma ALT activity, accompanied by a significant decrease in ALT activity in the liver, although CCl4 treatment alone had no significant effect on plasma ALT activity. A similar effect of VMH stimulation on plasma ALT activity was observed in rats treated with DMN, another hepatotoxic chemical. No such exaggerated effect of VMH stimulation on plasma ALT activity was observed after stimulation of the lateral hypothalamic area (LH). Surgical sympathetic denervation of the liver greatly suppressed the increase in plasma ALT activity after CCl4 injection and VMH stimulation. Measurement of regional blood flow indicated that VMH stimulation did not produce a significant change in blood flow to the liver. These results suggest that the VMH is involved in the progress of chemically-induced liver injury through activation of the sympathetic nerve (hepatic nerves), possibly by affecting liver metabolism more than the blood flow change to the liver.     

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

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 (Pdo), portal venous resistance (Rpv) and hepatic venous resistance (Rhv) were calculated. An antigen injection caused venoconstriction characterized by an increase in Rpv greater than Rhv and was accompanied by a large liver weight gain. Pretreatment with the NO synthase inhibitor NG-nitro-l-arginine methyl ester, but not the heme oxygenase inhibitor zinc protoporphyrin IX, potentiated the antigen-induced venoconstriction by increasing both Rpv 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.