The use of low doses of dopamine in intensive care medicine

The dopamine alpha- and beta-adrenoceptor dose-response curves are investigated in four patients who are exempt from cardiovascular disease. A dose-related increase in CO, HR and SV is observed with infusion rates of up to 3 micrograms kg-1 min-1. With concentrations greater than 10 micrograms kg-1 min-1, both BP and SVR increase. Low-dose dopamine infusion less than 3 micrograms kg-1 min-1 is investigated in ten other patients. With this infusion rate, a selective renal vasodilation is induced without peripheral or cardiac beta-adrenoceptor activation. Dopamine is responsible for an increase in diuresis FENa, GFR and RBF. These properties are indicated in renal failure, and when haemodynamic support is required in cardiac failure, if an infusion rate of up to 10 micrograms kg-1 min-1 is able to reverse cardiac insufficiency.     

Role of beta-adrenergic agonists in the control of vascular capacitance

The role of beta-adrenergic agonists, such as isoproterenol, on vascular capacitance is unclear. Some investigators have suggested that isoproterenol causes a net transfer of blood to the chest from the splanchnic bed. We tested this hypothesis in dogs by measuring liver thickness, cardiac output, cardiopulmonary blood volume, mean circulatory filling pressure, portal venous, central venous, pulmonary arterial, and systemic arterial pressures while infusing norepinephrine (2.6 micrograms.min-1.kg-1), or isoproterenol (2.0 micrograms.min-1.kg-1), or histamine (4 micrograms.min-1.kg-1), or a combination of histamine and isoproterenol. Norepinephrine (an alpha- and beta 1-adrenergic agonist) decreased hepatic thickness and increased mean circulatory filling pressure, cardiac output, cardiopulmonary blood volume, total peripheral resistance, and systemic arterial and portal pressures. Isoproterenol increased cardiac output and decreased total peripheral resistance, but it had little effect on liver thickness or mean circulatory filling pressure and did not increase the cardiopulmonary blood volume or central venous pressure. Histamine caused a marked increase in portal pressure and liver thickness and decreased cardiac output, but it had little effect on the estimated mean circulatory filling pressure. Isoproterenol during histamine infusions reduced histamine-induced portal hypertension, reduced liver size, and increased cardiac output. We conclude that the beta-adrenergic agonist, isoproterenol, has little influence on vascular capacitance or liver volume of dogs, unless the hepatic outflow resistance is elevated by agents such as histamine.     

Chronic hepatic artery ligation does not prevent liver from differentiating portal vs. peripheral glucose delivery

Infusion of glucose into the hepatic artery blocks the stimulatory effect of the "portal signal" on net hepatic glucose uptake (NHGU) during portal glucose delivery. We hypothesized that hepatic artery ligation (HAL) would result in enhanced NHGU during peripheral glucose infusion because the arterial glucose concentration would be perceived as lower than that in the portal vein. Fourteen dogs underwent HAL approximately 16 days before study. Conscious 42-h-fasted dogs received somatostatin, intraportal insulin, and glucagon infusions at fourfold basal and at basal rates, respectively, and peripheral glucose infusion to create hyperglycemia. After 90 min (period 1), seven dogs (HALpo) received intraportal glucose (3.8 mg. kg-1. min-1) and seven (HALpe) continued to receive only peripheral glucose for 90 min (period 2). These two groups were compared with nine non-HAL control dogs (control) treated as were HALpe. During period 2, the arterial plasma insulin concentrations (24 +/- 3, 20 +/- 1, and 24 +/- 2 microU/ml) and hepatic glucose loads (39.1 +/- 2.5, 43.8 +/- 2.9, and 37.7 +/- 3.7 mg. kg-1. min-1) were not different in HALpe, HALpo, and control, respectively. HALpo exhibited greater (P < 0.05) NHGU than HALpe and control (3.1 +/- 0.3, 2.0 +/- 0.4, and 2.0 +/- 0.1 mg. kg-1. min-1, respectively). Net hepatic carbon retention was approximately twofold greater (P < 0.05) in HALpo than in HALpe and control. NHGU and net hepatic glycogen synthesis during peripheral glucose infusion were not enhanced by HAL. Even though there exists an intrahepatic arterial reference site for the portal vein glucose concentration, the failure of HAL to result in enhanced NHGU during peripheral glucose infusion suggests the existence of one or more comparison sites outside the liver.     

Effect of adenosine and glucagon on hepatic blood volume responses to sympathetic nerves

Hepatic blood volume responses were studied in cats using in vivo plethysmography. The maximal response (Rmax) to sympathetic nerve stimulation and to infusions of norepinephrine into the hepatic artery or portal vein was similar (12-14 mL expelled per liver in 2.9-kg cats; average liver weight, 76.8 +/- 6.8 g). The ED50 for norepinephrine intraportal (0.44 +/- 0.13) and intrahepatic arterial infusions (0.33 +/- 0.08 micrograms.kg-1.min-1) were similar indicating equal access of both blood supplies to the capacitance vessels. Adenosine (2.0 mg.kg-1.min-1) did not cause significant volume changes but produced a mild (27%) suppression of Rmax due to nerve stimulation with no change in the frequency (3.4 Hz) needed to produce 50% of Rmax. Rmax tended (not statistically significant) to decrease during glucagon (1.0 micrograms.kg-1.min-1) infusion but the nerve frequency needed to produce 50% of Rmax rose to 5.6 Hz. Thus both adenosine and glucagon produced modulation of sympathetic nerve-induced capacitance responses without having significant effects on basal blood volume. Adenosine, by virtue of its marked effects on arterial resistance vessels (at substantially lower doses than those used here) and the relative lack of effect on venous capacitance vessels, may be useful for producing clinical afterload reduction without venous pooling.     

Comparative effects of dopamine and dobutamine on glucoregulation in a rat model.

The influence of dopamine as compared with dobutamine on glucose homeostasis has been assessed in thyroidectomized euthyroid rats. Both sympathomimetic agents were given intravenously over 6 h at four dosages, varying from 2 to 30 micrograms.kg-1.min-1. Immediately before the end of the infusion period, serum concentrations of glucose and insulin as well as plasma glucagon concentrations were measured. Dobutamine infusions did not exert any influence on these parameters. At a dose of 7.5 micrograms.kg-1.min-1, dopamine infusion caused a decrease in glucose concentrations, accompanied by a rise of glucagon and insulin levels. Glucose levels were significantly increased in the presence of unaltered insulin and decreasing glucagon levels at higher dopamine doses. The rise in glucose levels was reversed by 8 micrograms.kg-1.min-1 and inverted to a decrease by 12 micrograms.kg-1.min-1 of the alpha-adrenergic blocking agent phentolamine, simultaneously infused with 15 micrograms.kg-1.min-1 dopamine, while the insulin levels were increased and glucagon levels remained elevated. These findings demonstrate that dopamine acts on glucoregulation divergently, according to the dosage applied. The data suggest that dopamine rather than dobutamine treatment may disturb glucose homeostasis.     

Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic shock.

Gut metabolism may become anaerobic before the whole body during progressive phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator effects, we asked whether dopamine could delay onset of bowel ischemia during hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2 delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group of seven pigs received equivalent saline infusion. Onset of ischemia in whole body and gut was determined as critical O2 delivery (QO2c), the intersection point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2 extraction were measured as mechanisms of gut ischemia for entire in situ small and large gut using a superior mesenteric venous fistula. Dopamine hastened onset of gut ischemia relative to onset of whole body ischemia (gut critical point in terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7 ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in control animals occurred at same time as onset of whole body ischemia (gut critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset of gut ischemia in dopamine-treated animals was associated with decreased ability of gut to extract O2. Low-dose dopamine was not protective against gut ischemia during shock but rather caused earlier onset of gut ischemia during hemorrhagic shock.     

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)     

Hyperglycemic effect of high doses of dobutamine in the rat: studies of insulin and glucagon secretion

The influence of dobutamine on glucoregulation has been assessed in the rat during and after an intravenous infusion given at the following doses: 0, 0.1, 1.0, 10, 100, and 1000 micrograms X kg-1 X min-1. Plasma glucose, insulin, and glucagon levels were measured at 15-min intervals in unanesthetized previously cannulated rats. Basal glucose levels were preserved with the less than or equal to 10 micrograms X kg-1 X min-1 doses. At the greater than or equal to 100 micrograms X kg-1 X min-1 doses, a marked hyperglycemic effect was observed, partly attributable to some inhibitory effect of dobutamine on glucose-induced insulin secretion and to its stimulatory effect on glucagon secretion. Such data suggest that dobutamine may disturb the normal glucose homeostasis, particularly in situations of deficient insulin reserve.     

Atrial natriuretic factor release during acute infusion of isoproterenol in the conscious rat.

The effect of beta-adrenergic stimulation on atrial natriuretic factor (ANF) release was studied in conscious rats. 20-min infusion of 85 or 850 ng kg-1 min-1 isoproterenol (ISO) resulted in positive inotropic and chronotropic responses and no elevation of atrial pressures. A slight increase in plasma ANF, together with a drop in blood pressure, were observed only in the group infused with the higher dose. During the infusion of 850 ng kg-1 min-1 ISO, there was no relationship between plasma ANF and any of the haemodynamic parameters, with the exception of mean arterial pressure (r = 0.72, P less than 0.05, n = 9). Larger doses (greater than 3 micrograms kg-1 min-1) were toxic. We conclude that beta-adrenergic stimulation is not an important stimulus for ANF release when diastolic resting tension is low.     

Salutary effects of the prostacyclin analogue CG 4203 in lethal endotoxemia in rats

In pentobarbitone anesthetized rats infusion of E. coli endotoxin (0.42 mg.kg-1.min-1 for 4 hours) produced 96% lethality within 6 hours. Transient decrease in mean arterial blood pressure, thrombocytopenia, leukopenia, loss of plasma fibrinogen, fibrin deposits in renal glomeruli, hemolysis and decrease in arterial oxygen tension and pH were observed. Infusion of the prostacyclin analogue CG 4203 (0.464 and 1.0 micrograms.kg-1.min-1 for 6 hours), starting concomitantly with the endotoxin infusion, improved the survival rate to 95 and 100%. Blood pressure during endotoxemia was slightly lower in CG 4203 treated rats than in vehicle controls. CG 4203 infusion marginally attenuated thrombocytopenia and obviously inhibited leukopenia, but did not effect fibrinogen consumption in endotoxemic rats. Incidence of glomerular fibrin deposits was dose dependently and significantly reduced by CG 4203. The lower dose reduced and the higher dose completely prevented the occurrence of hemolysis. Acidotic changes were not observed in CG 4203 treated endotoxin-shocked rats. Also with treatment starting 1 hour after the onset of endotoxemia CG 4203 in the same doses significantly inhibited the endotoxin-induced lethality. As protective mechanisms against lethal rat endotoxemia the prostacyclin-like hemodynamic, fibrinolytic, rheological and membrane stabilizing properties of CG 4203 are discussed.     

Dynamics of hepatic lactate and glucose balances during prolonged exercise and recovery in the dog

The present experiments were undertaken to assess dynamics of hepatic lactate and glucose balance in the over-night-fasted dog during 150 min of moderate-intensity treadmill exercise and 90 min of exercise recovery. Catheters were implanted chronically in an artery and portal and hepatic veins 16 days before experimentation. 3-3H-glucose was infused to determine hepatic glucose uptake, as well as tracer-determined glucose production by isotope dilution (Ra). At rest, net hepatic lactate output was 0.33 +/- 0.15 mg.kg-1.min-1 and increased to 2.26 +/- 0.82 mg.kg-1.min-1 after 10 min of exercise, after which it fell such that the liver was a net lactate consumer by the end of exercise and through recovery. In contrast to the rapid release of lactate, net hepatic glucose output rose gradually from 2.58 +/- 0.20 mg.kg-1.min-1 at rest to 8.87 +/- 0.85 mg.kg-1.min-1 after 60 min of exercise, beyond which it did not change significantly until the cessation of exercise. Hepatic glucose uptake at rest was 1.38 +/- 0.42 mg.kg-1.min-1 and did not change appreciably during exercise or recovery. Absolute hepatic glucose output (net glucose output plus uptake) rose from 3.96 +/- 0.45 mg.kg-1.min-1 at rest to 10.20 +/- 1.09 mg.kg-1.min-1 after 60 min of exercise and was 9.65 +/- 1.15 mg.kg-1.min-1 at 150 min of exercise. Ra rose from 3.34 +/- 0.21 mg.kg-1.min-1 to 7.58 +/- 0.73 and 8.59 +/- 0.77 mg.kg-1.min-1 at 60 and 150 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebokrast as a corrector of postischemic phenomena in acute transient cerebral ischemia]

Acute cerebral ischemia in cats (both carotid arteries occlusion during 30 min after permanent occlusion of both vertebral arteries) was accompanied by postischemic hypoperfusion and hypo-oxygenation of the cerebral tissue. Intravenous infusion of cerebrocrast (1 micrograms.kg-1.min-1 during 60 min) prevented manifestation of the postischemic phenomena. Antihypoxic effect of cerebrocrast involved the cerebral blood flow increase, brain oxygen consumption lowering and Hb-O2-affinity decrease.     

Unlike mice, dogs exhibit effective glucoregulation during low-dose portal and peripheral glucose infusion

Portal infusion of glucose in the mouse at a rate equivalent to basal endogenous glucose production causes hypoglycemia, whereas peripheral infusion at the same rate causes significant hyperglycemia. We used tracer and arteriovenous difference techniques in conscious 42-h-fasted dogs to determine their response to the same treatments. The studies consisted of three periods: equilibration (100 min), basal (40 min), and experimental (180 min), during which glucose was infused at 13.7 micromol.kg(-1).min(-1) into a peripheral vein (p.e., n = 5) or the hepatic portal (p.o., n = 5) vein. Arterial blood glucose increased approximately 0.8 mmol/l in both groups. Arterial and hepatic sinusoidal insulin concentrations were not significantly different between groups. p.e. exhibited an increase in nonhepatic glucose uptake (non-HGU; Delta8.6 +/- 1.2 micromol.kg(-1).min(-1)) within 30 min, whereas p.o. showed a slight suppression (Delta-3.7 +/- 3.1 micromol.kg(-1).min(-1)). p.o. shifted from net hepatic glucose output (NHGO) to uptake (NHGU; 2.5 +/- 2.8 micromol.kg-1.min-1) within 30 min, but p.e. still exhibited NHGO (6.0 +/- 1.9 micromol.kg(-1).min(-1)) at that time and did not initiate NHGU until after 90 min. Glucose rates of appearance and disappearance did not differ between groups. The response to the two infusion routes was markedly different. Peripheral infusion caused a rapid enhancement of non-HGU, whereas portal delivery quickly activated NHGU. As a result, both groups maintained near-euglycemia. The dog glucoregulates more rigorously than the mouse in response to both portal and peripheral glucose delivery.     

Pulmonary vasodilator responses to atrial natriuretic factor and sodium nitroprusside

The objective of this study was to determine the direct actions of atrial natriuretic factor (ANF) on the pulmonary vascular bed and to compare these actions with those of sodium nitroprusside (SNP). The responses to incremental infusion rates of 1, 5, 10, and 50 ng.kg-1.min-1 synthetic human ANF and to 1-2 micrograms.kg-1.min-1 SNP were examined in the in situ autoperfused lung lobe of open-chest anesthetized pigs under conditions of normal and elevated pulmonary vascular tone. During basal conditions, ANF and SNP caused small but significant reductions in pulmonary artery pressure (Ppa) and pulmonary venous pressure (Ppv) with no change in lobar vascular resistance (LVR). When pulmonary vascular tone was increased by prostaglandin F2 alpha (20 micrograms/min), ANF infusion at doses greater than 1 ng.kg-1.min-1 decreased Ppa and LVR in a dose-related fashion. Infusion of 50 ng.kg-1.min-1 ANF and of 2 micrograms.kg-1.min-1 SNP maximally decreased Ppa, from 33 +/- 3 to 20 +/- 2 mmHg (P less than 0.001) and from 31 +/- 4 to 18 +/- 1 mmHg (P less than 0.001), respectively. At these doses, ANF reduced systemic arterial pressure by only 11.5 +/- 3% compared with 34 +/- 4% decreased with SNP (P less than 0.001). The results indicate that ANF, similarly to SNP, exerts a direct potent vasodilator activity in the porcine pulmonary vascular bed, which is dependent on the existing level of vasoconstrictor tone.     

Failure of hyperketonemia to alter basal and insulin-mediated glucose metabolism in man

The effect of physiologic elevations of plasma hydroxybutyrate induced by the infusion of sodium D,L-beta-hydroxybutyrate (15 mumol X kg-1 X min-1) on carbohydrate metabolism was examined with the euglycemic insulin clamp technique in nine healthy volunteers. Plasma insulin concentration was acutely raised and maintained at 126 +/- 6 microU/ml and plasma glucose was held constant at the fasting level by a variable glucose infusion. Glucose uptake of 6.53 +/- 0.80 mg X kg-1 X min-1 was unchanged by hyperketonemia when compared with an intraindividual control study using saline instead of beta-OH-butyrate infusion (6.26 +/- 0.59 mg X kg-1 X min-1). In studies, in which the degree of metabolic alkalosis accompanying butyrate infusion was mimicked by the continuous administration of bicarbonate, glucose uptake was also unaffected (6.25 +/- 0.45 mg X kg-1 X min-1). Furthermore, hyperketonemia had no effect on basal glucose production or the suppression of hepatic glucose production following hyperinsulinemia. It is concluded that moderate elevations in plasma beta-hydroxy-butyrate do not alter hepatic or peripheral glucose metabolism.     

Method for measuring hepatic uptake of oxygen or other blood-borne substances in situ.

A preparation is described by which hepatic arterial blood flow and portal venous blood flow can be accurately and continuously measured while simultaneously providing a method by which multiple blood samples can be taken from the hepatic artery, portal vein, and hepatic vein without disrupting hepatic hemodynamics or causing hemodilution. By this means hepatic uptake or release of blood-borne substances can be measured in situ and correlated with hemodynamic parameters. In 13 splenectomized cats, oxygen uptake by the denervated liver was 4.5 +/- 0.3 ml . min-1. 100 g-1 of tissue, representing 54% of total oxygen removed by the splanchnic bed. The hepatic hemodynamics determined by this method are similar to those reported by others in vivo and the metabolic state of the liver remained stable for at least 2 h during which an average of 29 blood samples were taken. Advantages of this preparation over other methods of obtaining similar data are discussed.     

Pressor inhibition of angiotensin-induced ACTH secretion

We investigated whether the pressor effects of systemically administered angiotensin II (AII) influence ACTH secretion. Adrenalectomized barbiturate-anesthetized mongrel dogs with constant low resting cortisol concentrations due to slow constant cortisol infusion received either bolus injections (2.5 micrograms kg-1) or 15-min i.v. infusions of a low dose (12.5 ng kg-1min-1) of AII during which blood samples were taken for ACTH and cortisol determinations. In sequential continuous experiments in each dog, blood pressure was allowed to increase in response to AII administration or was controlled by means of concurrent i.v. injections or infusions of the hypotensive drug papaverine, or by blood withdrawal from the vena cava. When the arterial pressure rise induced by AII was substantially attenuated or prevented by papaverine administration or blood withdrawal, mean ACTH secretion rates increased 400-800% and mean ACTH concentrations increased by 280-500%. On the other hand, AII administration alone caused large increases in mean arterial blood pressure but did not increase ACTH secretion significantly above control levels. These data suggest that when endogenous AII levels are elevated without a concurrent increase in blood pressure, as occurs during hypovolemia or sodium depletion, AII may have a significant influence on ACTH secretion.     

Progressive weakening of the response of key enzymes of liver glycogen metabolism to permanently increased plasma epinephrine levels

In adult male rats anaesthetized with pentobarbital the intravenous infusion of 0.5 micrograms.kg-1.min-1 of epinephrine increased liver phosphorylase a activity within 5 min, whereas later a weakening of the hormone effect was observed. After increasing the infusion rate to 1.0 micrograms.kg-1.min-1 and extending the study to more parameters, the diminishing effect on phosphorylase was confirmed and a similar response was established for liver cAMP. Concomitantly, a decrease and recovery of liver glycogen synthase a activity was observed. In rats with permanent catheters in one of their tail arteries for obtaining blood samples, the plasma epinephrine levels were shown to be permanently increased (from cca 1 pmol.ml-1 before infusion of 1.0 micrograms.kg-1.min-1 to more than 30 pmol.ml-1 during infusion) and remained at steady levels throughout the infusion. Therefore, the weakening of the epinephrine effect should be ascribed to changes at (or beyond) the catecholamine receptor level. A hitherto undescribed decrease of total glycogen synthase activity was observed during the infusions.     

Quantitative proton nuclear magnetic resonance of plasma for screening hepatic metabolism during ethanol infusion in cats

The effects of increasing blood ethanol levels on hepatic metabolism were studied in anesthetized cats whose prior fluid intake contained ethanol for 24 days. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of blood volume. For ethanol, Vmax was 106 +/- 15 mumol.min-1.100 g-1 liver and Km was 164 +/- 31 microM. A previous study showed that there were no changes in O2 uptake by the liver, suggesting other oxidative processes were suppressed during ethanol metabolism. In this study, proton nuclear magnetic resonance spectroscopy was used to simultaneously screen several plasma metabolites to elucidate other metabolic processes that may be perturbed in the liver during ethanol infusion. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose above 0.5 Vmax. Thus, lactate oxidation is one process that can be suppressed to allow ethanol oxidation without additional O2 uptake by the liver. In addition, no release of acetate from the liver occurred during ethanol metabolism in these experiments. This surprising finding suggests ethanol metabolism may, under some conditions or in some species, result in fatty acid synthesis rather than acetate release. Eight other major metabolites remained unchanged during ethanol infusion.     

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.