Hepatic Arterial Vascular Resistance Research Articles

A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl4-cirrhotic liver

Increase of portal venous vascular resistance is counteracted by decrease of hepatic arterial vascular resistance (hepatic arterial buffer response). This process is mediated by adenosine in normal livers. In cirrhosis, hepatic arterial vascular resistance is decreased but the involvement of adenosine in this process is unknown. The aim of our study was to identify the signalling pathway responsible for the decreased hepatic arterial resistance in cirrhotic livers. Cirrhosis was induced by CCl(4). Using a bivascular liver perfusion dose-response curves to adenosine of the HA were performed in the presence and the absence of pan-adenosine blocker (8-SPT), A1 blocker (caffeine) or nitric oxide synthase-blocker (l-NMMA) after preconstriction with an alpha1-agonist (methoxamine). Western blot of the HA were used to measure the density of the A1 and A2a receptors. Adenosine caused a dose dependent relaxation of the hepatic artery of both cirrhotic and control animals that were blocked in both groups by 8-SPT (P<0.02). The response to adenosine was greater in cirrhotic rats (P=0.016). Both l-NMMA (P=0.003) and caffeine reduced the response to adenosine in cirrhotic but not in control animals. Western blot analysis showed a higher density of A1 and a lower density of A2a receptor in cirrhotic animals (P<0.05). The adenosine-induced vasodilatation of the HA is increased in cirrhotic rats suggesting a role for adenosine-NO in the decreased hepatic arterial vascular resistance found in cirrhosis. This significantly greater response in cirrhosis by the A1 receptor follows the same pathway that is seen in hypoxic conditions in extra-hepatic tissues.

Nitric oxide and vascular remodeling modulate hepatic arterial vascular resistance in the isolated perfused cirrhotic rat liver

Hepatic arterial resistance is modulated by the hepatic arterioles but the role of NO and vascular remodeling in hepatic arterial resistance in cirrhosis is unknown. Cirrhosis was induced by CCl(4) or BDL. Using a bivascular liver perfusion dose-responses curves to methoxamine were obtained from the hepatic artery in absence and presence of L-NMMA. Lumen-diameter, wall thickness and number of smooth muscle nuclei were quantitated in the arteries using image analysis. Hepatic arterial resistance and the response to methoxamine were lower in cirrhosis compared to controls (p< or = 0.04) and lower in BDL compared to CCl(4) (p< or = 0.01). L-NMMA increased the response to methoxamine in CCl(4) (p=0.002) and BDL (p=0.05) but corrected the response only in CCl(4) (p=n.s. vs. control). Wall thickness and the number of smooth muscle nuclei were significantly smaller in cirrhosis compared to controls (p<0.05) and the number of nuclei was also lower in BDL compared to CCl(4) (p=0.005). NO is the main modulator of hepatic arterial resistance in CCl(4) but not in BDL. Intrahepatic arterial remodeling is present in both cirrhotic models but is greater in BDL. This indicates a larger role of structural changes in the control of hepatic arterial resistance in BDL.

Hepatolobectomy-induced depression of hepatic circulation and metabolism in the dog is counteracted by isoflurane, but not by halothane.

The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection. Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n = 12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time. Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy. The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases.

Prevention of the hemorrhagic hypotension-induced hepatic arterial vasoconstriction by L-arginine and naloxone.

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Hepatic arterial pulsatility index in cirrhosis: correlation with portal pressure

Background/Aims: Determination of the pulsatility index by means of duplex sonography provides the opportunity to evaluate the vascular resistance of the hepatic artery noninvasively. The aim of this study was to investigate the relationship between the hepatic arterial pulsatility index and the hepatic venous pressure gradient in cirrhosis. Methods: In 50 patients with cirrhosis, hepatic venous pressure gradient was determined in the fasting state. Immediately thereafter, hepatic arterial pulsatility index and portal blood flow velocity were measured by duplex sonography with no knowledge of hepatic venous pressure values. In addition, the duplex parameters were determined in 20 controls. Results: Hepatic arterial pulsatility index was significantly higher in patients with cirrhosis than in controls (0.92±0.1 vs. 1.14±0.18; p<0.001) and directly correlated with the hepatic venous pressure gradient ( r=0.7; p<0.001). Furthermore, weak correlations were found between hepatic arterial pulsatility index and Child-Pugh score ( r=0.49; p<0.01) and between portal blood flow velocity and hepatic venous pressure gradient ( r=−0.48; p<0.01). Conclusion: In cirrhosis the hepatic arterial vascular resistance seems to increase parallel to the rise of the portal pressure. Therefore, duplex sonographic determination of the hepatic arterial pulsatility index may contribute to the noninvasive evaluation of portal hypertension.

Differential regulation of hepatic arterial and portal venous vascular resistance by nitric oxide and carbon monoxide in rats

Nitric oxide (NO), a gaseous mediator that accounts for the biological activity of endothelium-derived relaxing factor, has been shown to play an important role in the reduction of basal vascular tone in multiple vascular beds, including the hepatic circulation. On the other hand, recent studies have provided first evidence that endogenously generated carbon monoxide (CO) may exert vasodilatory effects in the hepatic portal vein and within sinusoids. Thus, we defined the differential role of NO and CO in the regulation of vascular resistance in the two inflows to the liver in the normal rat in vivo. Male Sprague-Dawley rats were anesthetized with pentobarbital sodium and surgically instrumented in order to study the change in hepatic arterial (R ha and portal venous vascular resistance (R pv) in response to intravenous bolus administration of either the NO-synthase inhibitor N ω-nitro-L-arginine methyl ester (L-NAME) (1 mg/kg; n = 7 animals) or of tin protoporphyrin-IX (SnPP-IX) (50 μmol/kg), a specific inhibitor of the CO-generating enzyme heme oxygenase (n = 8 animals). While L-NAME caused a substantial increase in R ha, R pv increased only slightly under these conditions. In sharp contrast, SnPP-IX did not affect R ha, but caused a profound increase in R pv. In conclusion, R ha and R pv are differentially regulated by NO and CO in the normal rat liver in vivo, i.e., NO serves as a potent vasodilator in the hepatic arterial circulation, but exerts only a minor vasodilatory effect in the portal venous vascular bed. In contrast, while there is no intrinsic CO-mediated vasodilation in the hepatic artery, CO acts to maintain portal venous vascular tone in a relaxed state.

Effects of sevoflurane and halothane anesthesia on liver circulation and oxygen metabolism in the dog during hepatolobectomy

Effects of sevoflurane and halothane anesthesia on liver circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, with the aim of choosing a better anesthetic for hepatic resection. Sixteen mongrel dogs were randomly divided into two groups with eight in each. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows (1) before the inhalation of each anesthetic (base line); (2) 1 h after the start of inhalation of 1.5 minimum alveolar concentration (MAC) anesthetic; (3) 1 h after hepatolobectomy with the same MAC of anesthesia; and (4) 2 h after the discontinuation of anesthesia. Measurements of systemic hemodynamics, blood gas tensions, plasma enzyme leaks and arterial ketone body ratio were made at the same time. Sevoflurane maintained hepatic arterial blood flow better than halothane anesthesia, both before and after hepatolobectomy. Hepatic arterial vascular resistance increased in the halothane group but did not change in the sevoflurane group after hepatolobectomy. No significant difference was found in oxygen metabolism and arterial ketone body ratio between two groups. Serum enzyme leakage was less in the sevoflurane group. Sevoflurane has less adverse effects on liver circulation, especially hepatic arterial blood flow, and hepatic function than halothane in the case of hepatolobectomy.

The transhepatic response to noradrenaline in the rabbit liver: the influence of arterioportal pressure gradient.

The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10(-10)-10(-4) mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline. At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68.5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged. These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance.

The Effects of Sevoflurane, Halothane, Enflurane, and Isoflurane on Hepatic Blood Flow and Oxygenation in Chronically Instrumented Greyhound Dogs

Inhalational anesthetics produce differential effects on hepatic blood flow and oxygenation that may impact hepatocellular function and drug clearance. In this investigation, the effects of sevoflurane on hepatic blood flow and oxygenation were compared with those of enflurane, halothane, and isoflurane in ten chronically instrumented greyhound dogs. Each dog randomly received enflurane, halothane, isoflurane, and sevoflurane, each at 1.0, 1.5, and 2.0 MAC concentrations. Mean arterial blood pressure and cardiac output decreased in a dose-dependent fashion during all four anesthetics studied. Heart rate increased compared to control during enflurane, isoflurane, and sevoflurane anesthesia and did not change during halothane anesthesia. Hepatic arterial blood flow and portal venous blood flow were measured by chronically implanted electromagnetic flow probes. Hepatic O2 delivery and consumption were calculated after hepatic arterial, portal venous, and hepatic venous blood gas analysis. Hepatic arterial blood flow was maintained with sevoflurane and isoflurane. Halothane and enflurane reduced hepatic arterial blood flow during all anesthetic levels compared to control (P less than 0.05), with marked reductions occurring with 1.5 and 2.0 MAC halothane concomitant with an increase in hepatic arterial vascular resistance. Portal venous blood flow was reduced with isoflurane and sevoflurane at 1.5 and 2.0 MAC. A somewhat greater reduction in portal venous blood flow occurred during 2.0 MAC sevoflurane (P less than 0.05 compared to control and 1.0 MAC values for sevoflurane). Enflurane reduced portal venous blood flow at 1.0, 1.5, and 2.0 MAC compared to control. Halothane produced the greatest reduction in portal venous blood flow (P less than 0.05 compared to sevoflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

PAF increases hepatic vascular resistance and glycogenolysis in vivo

Administration of platelet-activating factor (PAF) to portal venous circulation of anesthetized fed rats produced decreases in mean arterial pressure and increases in hepatic portal pressure and blood glucose concentration. These responses to PAF were dose dependent with ED50 values of 0.02-0.05 micrograms/kg and specific as lyso- and enantio-PAF did not reproduce effects of PAF. Specific PAF receptor antagonist SRI 63-675 (75 micrograms/kg) inhibited significantly these PAF (0.1 micrograms/kg)-induced responses in rats. Administration of prazosin (500 micrograms/kg) and propranolol (400 micrograms/kg) to rats abolished phenylephrine (50 micrograms/kg)-induced increases in mean arterial pressure, hepatic portal pressure, and blood glucose concentration but did not prevent PAF (1 microgram/kg)-induced alterations in these parameters. Glycogen phosphorylase alpha levels were increased significantly in livers of rats after administration of PAF (1 microgram/kg) or phenylephrine (50 micrograms/kg). Administration of prazosin and propranolol to rats inhibited phenylephrine- but not PAF-induced activation of hepatic glycogen phosphorylase. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP) concentration was increased slightly by PAF, but these increases were eliminated by adrenergic blockade, suggesting that activation of hepatic glycogen phosphorylase by PAF is not dependent on increases in cAMP. Increases in hepatic portal pressure and blood glucose concentration in response to PAF (0.1 micrograms/kg) were not attenuated in adrenalectomized rats. Moreover, PAF (0.1 micrograms/kg) stimulated increases in hepatic portal pressure after administration of the ganglionic blocking agent chlorisondamine (2.5 mg/kg) to adrenalectomized rats. Administration of PAF (0.05 micrograms/kg) to rats instrumented with pulse Doppler flow probes produced decreases in hepatic arterial and portal vein blood flow and increases in hepatic arterial and portal vascular resistance. These observations provide direct evidence that PAF regulates hepatic hemodynamics and glycogenolysis in vivo. It is suggested that PAF plays an important role in regulating hepatic blood flow and supplying extrahepatic tissues with energy substrates by sympathetic-independent mechanism(s) after its release in acute pathophysiological situations.

Participation of adrenoceptors in liver blood flow regulation in anesthetized dogs.

We evaluated involvement of adrenergic receptors in the responses of the hepatic vasculature to reduction either of portal venous flow or hepatic arterial inflow. Portal vein occlusion caused an increase in hepatic arterial blood flow (HAF) and decreases in hepatic arterial pressure (HAP) and hepatic arterial vascular resistance (HAR) in the intact group. After pretreatment with either yohimbine or prazosin, but not propranolol, occlusion of the portal vein produced a greater decrease in HAP as compared with that in the intact group. No significant changes in HAF, HAR, or hepatic tissue blood flow (HTF) occurred after the treatment. These results indicate that the compensatory response of the hepatic arterial vasculature to altered portal blood flow (PVF) is regulated independently of the intrahepatic adrenergic receptors. Hepatic arterial occlusion caused a significant decrease in portal venous pressure, PVF, and HTF. Portal venous vascular resistance (PVR) was reduced slightly, but not significantly. After pretreatment with either yohimbine or prazosin, but not propranolol, occlusion of the hepatic artery produced an opposite effect: to increase PVF and significantly decrease PVR. These results indicate that intrahepatic alpha-adrenoceptors participate in the regulation of portal vascular tone to maintain portal vein pressure at a steady level, when inflow from the hepatic artery is reduced.

The effect of normothermic cardiopulmonary bypass on hepatic blood flow in the dog

Hepatic blood flow was investigated in two groups of eight anaesthetized dogs during and after one hour of either pulsatile or non-pulsatile cardiopulmonary bypass (CPB). Mean perfusion pressure was maintained at 60 mmHg. Hepatic arterial (HA) and portal venous (PV) blood flows were measured using electromagnetic flow probes, and hepatic O 2 consumption determined. The results demonstrate that: (a) pulsatile CPB reduces peripheral vascular resistance during and after perfusion, and more effectively preserves pump flow rate and cardiac output than non-pulsatile CPB; (b) total liver blood flow is sustained more effectively by pulsatile CPB than by non-pulsatile CPB due to relative preservation of both HA and PV flows; (c) hepatic O2 consumption is only marginally better preserved during and after pulsatile CPB than with non-pulsatile perfusion. We conclude that: (a) pulsatile CPB tends to maintain hepatic blood flow through a relative reduction in HA vascular resistance and an improvement in PV flow produced passively by a greater pump flow rate; (b) pulsatile CPB less effectively benefits hepatic O2 consumption because of poor O2 uptake from the hepatic PV blood supply.

Effect of propranolol on hepatic blood flow in patients with cirrhosis.

The effect of propranolol on systemic and hepatic hemodynamics was studied in patients with cirrhosis. One hour after 40 mg propranolol by mouth as well as during continuous oral dosing at doses that reduced heart rate 25%, cardiac output and the hepatic venous pressure gradient fell significantly, whereas arterial pressure and hepatic blood flow did not change significantly. In six patients with cirrhosis and surgical end-to-side portacaval shunts, cardiac output and the hepatic venous pressure gradient also decreased 15 minutes after intravenous propranolol (5 mg), whereas hepatic blood flow did not change significantly. In the patients with surgical shunts, systemic vascular resistance rose significantly but hepatic arterial vascular resistance fell. Our data show that in patients with cirrhosis, propranolol induces an increase in the fraction of cardiac output reaching the liver.

Acute effect of propranolol on splanchnic circulation in normal and portal hypertensive rats

Propranolol decreases portal venous pressure in patients with cirrhosis but no method is available in man to study the effect of this beta-blocker on splanchnic organ blood flow. Because in rats, the microsphere method allows evaluation of regional blood flow, the acute effect of propranolol on both splanchnic and systemic circulations was studied in normal rats and in rats with portal hypertension due to portal vein stenosis. Portal venous pressure significantly decreased during propranolol administration in normal (5.6 +/- 1.0-4.7 +/- 1.1 mm Hg; mean +/- SD) as well as in portal hypertensive rats (11.7 +/- 2.3-10.3 +/- 1.8 mm Hg). Propranolol slightly decreased cardiac output and arterial pressure in all rats. Portal tributary blood flow was significantly reduced by propranolol in normal rats (17.4 +/- 3.0-11.3 +/- 2.2 ml/min) and in portal hypertensive rats (23.7 +/- 5.0-16.6 +/- 3.3 ml/min). Accordingly vascular resistance of the different organs in the portal venous territory increased in these rats receiving propranolol. The percentage of the decrease in portal tributary blood flow was significantly more marked than the percentage of reduction in cardiac output in portal hypertensive rats but, in normal rats, these percentages were parallel. Hepatic arterial blood flow did not change or slightly increased and, consequently, hepatic arterial vascular resistance decreased. These findings further clarify the marked effects of propranolol on splanchnic circulation.

Central and splanchnic hemodynamics in the dog during controlled hypotension with adenosine.

Central and splanchnic hemodynamic effects during controlled hypotension induced by the administration of the endogenous vasodilator adenosine were studied in ten artificially ventilated dogs under neurolept anesthesia. Adenosine was administered as a continuous infusion in the aorta (n = 3), in the inferior vena cava (n = 3), and after pretreatment with dipyridamole (which inhibits the cellular uptake of adenosine) (n = 4) in a dose sufficient to maintain a mean arterial blood pressure (MABP) level of approximately 50 mmHg. Observations were made before and after 20 min of controlled hypotension. Basal arterial plasma levels of adenosine were in the 10(-7) M range (means = 0.4 microM). The hemodynamic response was similar in all three settings. Adenosine caused a profound decrease in systemic vascular resistance (SVR) (52%, P less than 0.01) and preportal vascular resistance (PPR) (64%, P less than 0.01), while hepatic arterial vascular resistance ( HAR ) increased by 49% (P less than 0.05). Cardiac output increased (22%, P less than 0.05) through increase of stroke volume (77%, P less than 0.01), while heart rate decreased (28%, P less than 0.01). Whole-body oxygen uptake decreased (14%, P less than 0.01). Portal venous blood flow increased by 28% (P less than 0.05), whereas hepatic arterial blood flow decreased by 70% (P less than 0.01). In the preportal tissues, oxygen uptake decreased by 21% (P less than 0.01). In contrast, hepatic oxygen consumption increased (53%, P less than 0.05). Adenosine-induced hypotension was not associated with changes in plasma renin activity or the plasma concentration of norepinephrine. It is concluded that adenosine causes a rapidly induced and easily maintained hypotension and may be a potentially useful agent for controlled hypotension in patients.

The hepatic haemodynamic response to acute portal venous blood flow reductions in the dog.

The hepatic haemodynamic response to acute reductions in portal venous blood flow was investigated in 14 anaesthetized normal dogs. A side-to-side mesocaval anastomosis was constructed to enable varying degrees of portal flow to be diverted into the inferior vena cava by suitable manipulations of the shunt diameter. Measurements of portal venous and hepatic arterial blood flow were made with electromagnetic flowmeters. A linear relationship was observed between the degree of reduction in portal flow and the magnitude of the resulting hepatic arterial hyperaemic response. Hepatic arterial vascular resistance showed a decrease which became more pronounced the greater the degree of reduction in portal flow. For every 1.0 ml X min-1 100 g-1 decrease in portal flow, the hepatic arterial flow increased by a mean of 0.24 ml X min-1 X 100 g-1, a value representing the average compensatory capacity of the arterial response. Arterial flow improvement therefore provided some degree of protection against severe falls in total liver blood flow. However, it provided even more effective protection against any fall in total hepatic oxygen consumption, which showed only a very gradual decrease with reduced hepatic portal blood flow.

Adjustments of hepatic and small intestine blood flow on selective vasoconstrictor fibre stimulation.

The mutual changes in hepatic and small intestinal blood flow on selective nervous stimulation of the periarterial vasoconstriction fibres, were studied in anaesthetized cats. Occlusion of the hepatic artery did not change portal blood flow, whereas occlusion of superior mesenteric blood flow caused a significant increase in hepatic arterial flow. Stimulation of the hepatic sympathetic nervous supply caused a phasic blood flow response with a marked transient peak flow reduction of hepatic arterial blood flow. The magnitude of the peak response varied with the frequency of the stimulation. Despite continuous stimulation the first phase went over into a second phase of less pronounced vasoconstriction. This "steady state" blood flow, was maintained at about 20% below the control level, irrespective of stimulation frequency. Corresponding in time with the peak vasoconstriction there was a transient increase of portal pressure. Sympathetic nerve stimulation increased portal pressure even on occlusion of the hepatic artery. Stimulation of the mesenteric sympathetic nerves evoked the characteristic transient peak vasoconstrictor response consisting of two phases, a brief intense peak resistance response followed by a second phase of less pronounced but generally well maintained constriction. Simultaneously a slight reduction of portal pressure and hepatic arterial vascular resistance was regularly seen. In contrast to the observations in the hepatic arterial circuit the magnitude of this "steady state" blood flow in the small intestine was dependent on the rate of the stimulation, however. On simultaneous stimulation of the hepatic and mesenteric sympathetic nerves the hemodynamic responses were largely the same as when these nerves were stimulated separately. The portal pressure affecting mean capillary pressure in the intestine differed, however. Small and variable pressure changes were followed by rapid return towards control and during steady state it did not differ from the prestimulatory level.

Responses of the simultaneously-perfused hepatic arterial and portal venous vascular beds of the dog to histamine and 5-hydroxytryptamine.

1 The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. 2 Histamine and 5-hydroxytryptamine (5-HT) were injected intra-arterially and intraportally in graded, increasing doses. 3 Intra-arterial histamine evoked decreases in hepatic arterial vascular resistance (HAVR) and increases in hepatic portal vascular resistance (HPVR). 4 Intraportal injections of histamine caused increases in HPVR and decreases in HAVR. 5 The time courses of the arterial responses to intraportal histamine and of the portal responses to intra-arterial histamine, compared with any systemic effects, showed that these effects on the liver vasculature could not be the result of recirculation of histamine. 6 Intra-arterial 5-HT evoked biphasic changes in HAVR and small falls in HPVR. Intraportal 5-HT caused falls in HPVR at low doses and rises at high doses, together, typically, with biphasic effects on HAVR. 7 It is unlikely that the arterial effects of intraportal 5-HT and the portal effects of intra-arterial 5-HT were due to recirculation of the vasoactive material. 8 Pathophysiologically, both histamine and 5-HT are released from the gastrointestinal tract into the portal vein. These experiments show that such release may affect the hepatic arterial vascular resistance (and therefore blood flow) even though vasoactive levels of the autacoids are not attained in the systemic circulation.

Pressure-flow relationships and effects of noradrenaline and isoprenaline on the hepatic arterial and portal venous vascular beds of the dog.

1. The innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously, in situ. Under control conditions, the pressures, blood flows and calculated vascular resistances in these beds were similar to those previously reported in preparations where one bed was perfused alone. 2. The pressure-flow curves in both the hepatic arterial and portal venous vascular beds were almost linear over the pressure ranges 30--200 and 2.5--12.0 mmHg respectively. There was no evidence of pressure-induced autoregulation of flow in either circuit. 3. Increases in hepatic arterial blood flow and perfusion pressure were associated with a linearly related increase in hepatic portal vascular resistance. Occlusion of the hepatic artery caused a mean fall of 21.3% in portal vascular resistance. 4. Increases in hepatic portal blood flow and perfusion pressure were associated with a linearly related incease in hepatic arterial vascular resistance. Occlusion of the hepatic portal vein caused a mean fall of 16.0% in hepatic arterial vascular resistance. 5. Intra-arterial injections of noradrenaline (0.1--50 microgram) caused biphasic changes in hepatic arterial vascular resistance, and a rise in hepatic portal vascular resistance. Both hepatic vascular effects had a significantly shorter latency than any succeeding systemic cardiovascular effects. 6. Intraportal injections of noradrenaline (0.1--50 microgram) caused hepatic portal vasoconstriction, and a biphasic change in the hepatic arterial resistance. Both of these effects had a significantly shorter latency than any succeeding systemic effects. 7. Intra-arterial injections of isoprenaline (0.1--10 microgram) caused dose-dependent hepatic arterial vasodilatation but little change in portal vascular resistance. Intraportal isoprenaline caused little change in portal resistance but elicited dose-dependent hepatic arterial vasodilatation. 8. The time courses of the responses to intra-arterial and intraportal noradrenaline and isoprenaline indicate that the responses of the liver vascular bed which does not receive the direct injection were not due to recirculation of the vasoactive material. 9. It is postulated that vasoactive material injected into one inflow circuit of the liver elicits changes in the vascular resistance of the other inflow circuit by an intrahepatic effect.

The effects of intraportal infusions of glucagon on the hepatic arterial and portal venous vascular beds of the dog: inhibition of hepatic arterial vasoconstrictor reponses to noradrenaline.

The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. Glucagon was infused into the hepatic portal vein (1--10 microgram/min); it caused increases in hepatic portal vascular resistance and tended to reduce the hepatic arterial vascular resistance. Extrahepatic effects of intraportal infusions of glucagon included increases in superior mesenteric blood flow and heart rate and falls in systemic arterial pressure. A test dose of noradrenaline (10 microgram) injected into either the hepatic artery or the portal vein caused both hepatic arterial and portal venous vasoconstriction. The hepatic arterial constrictor responses to noradrenaline were antagonized by intraportal infusions of glucagon. In contrast, intraportal glucagon did not antagonize the portal constrictor responses to intraarterial or intraportal noradrenaline. Elevated portal blood glucagon concentrations may "protect" the hepatic arterial blood flow from vasoconstriction due to elevated systemic levels of vasoactive substances including catecholamines.