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After a meal, glucagon-like peptide-1 (GLP-1) levels in the hepatic portal vein are elevated and are twice those in peripheral blood. The aim of this study was to determine whether any of GLP-1's acute metabolic effects are initiated within the hepatic portal vein. Experiments consisted of a 40-min basal period, followed by a 240-min experimental period, during which conscious 42-h-fasted dogs received glucose intraportally (4 mg x [kg.sup.-1] x [min.sup.-1]) and peripherally (as needed) to maintain arterial plasma glucose levels at ~160 mg/dl. In addition, saline was given intraportally (CON; n = 8) or GLP-1 (1 pmol x [kg.sup.-1] x [min.sup.-1]) was given into the hepatic portal vein (POR; n = 11) or the hepatic artery (HAT; n = 8). Portal vein plasma GLP-1 levels were basal in CON, 20x basal in POR, and 10x basal in HAT, whereas levels in the periphery and liver were the same in HAT and CON. The glucose infusion rate required to maintain hyperglycemia was significantly greater in POR (8.5 [+ or -] 0.7 mg x [kg.sup.-l] x [min.sup.-1], final 2 h) than in either CON or HAT (6.0 [+ or -] 0.5 or 6.7 [+ or -] 1.0 mg x [kg.sup.-l] x [min.sup.-1], respectively). There were no differences among groups in either arterial plasma insulin (24 [+ or -] 2, 23 [+ or -] 3, and 23 [+ or -] 3 [micro]U/ml for CON, POR, and HAT, respectively) or glucagon (23 [+ or -] 2, 30 [+ or -] 3, and 25 [+ or -] 2 pg/ml) levels during the experimental period. The increased need for glucose infusion reflected greater nonhepatic as opposed to liver glucose uptake. GLP-1 infusion increased glucose disposal independently of changes in pancreatic hormone secretion but only when the peptide was delivered intraportally. dog; liver; glucagon-like peptide-1; hepatic portal vein

A variety of portal vein anomalies that occur in children can be identified by US, CT, MRI and portal venography. Although these abnormalities can also occur in adults, there are certain pathological processes and aberrations within the portal system that are specific to children. Knowledge of the embryology and anatomy of the portal vein is of benefit in the understanding of these anomalies. Identifying deviations from normal portal architecture is important in the work-up for surgery such as liver transplantation, and prior to interventional procedures such as stent placement or embolization. The aim of this paper is to summarize the various types of congenital and acquired portal vein abnormalities that occur in children, describe their radiological features and provide images to demonstrate the differences from normal portal venous anatomy. Keywords Portal vein anatomy * Congenital variations * Ultrasound * CT * MRI

Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PG[I.sub.2] production by enzyme immunoassay of 6-keto-PG[F.sub.1[alpha]] was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PG[F.sub.1[alpha]] was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension. vasodilator prostanoids; vascular hyporeactivity; resistance vessels; cyclooxygenase; mesenteric vascular bed; portal vein-ligated

Ion channels encoded by ether-a-go-go-related genes (ERG) have been implicated in repolarization of the cardiac action potential and also as components of the resting membrane conductance in various cells. The aim of the present study was to determine whether ERG channels were expressed in smooth muscle cells isolated from portal vein. RT-PCR demonstrated the expression of murine ERG (mERG), and real-time quantitative PCR showed that the mERG1b isoform predominated over the mERG1a, mERG2, and mERG3 in portal vein. Single myocytes from portal vein displayed membrane staining with an ERG1-specific antibody. Whole cell voltage-clamp experiments were performed to determine whether portal vein myocytes expressed functional ERG channels. Large inward currents with distinctive kinetics were elicited that were inhibited rapidly by E-4031 (mean amplitude of the E-4031-sensitive current at -120 mV was -205 [+ or -] 24 pA; n = 14). Deactivation of the E-4031-sensitive current was voltage dependent (mean time constants at -80 and -120 mV were 103 [+ or -] 9 and 33 [+ or -] 2 ms, respectively; n = 13). Because of the rapid kinetics of mERG currents at more negative potentials, there was a substantial noninactivating 'window' current that reached a maximum of -66 [+ or -] 10 pA at -70 mV. Complete portal veins exhibited spontaneous contractile activity in isometric tension experiments, and this activity was modified significantly by E-4031. These data show that ERG channels are expressed in murine portal vein myocytes that may contribute to the resting membrane conductance. vascular smooth muscle; ether-a-go-go-related genes; potassium channel

Agonist-induced activation of smooth muscle involves a rise in intracellular [Ca.sup.2+] concentration and sensitization of myosin light chain phosphorylation to [Ca.sup.2+]. [Sr.sup.2+] can enter through [Ca.sup.2+] channels, be sequestered and released from sarcoplasmic reticulum, and replace [Ca.sup.2+] in activation of myosin light chain phosphorylation. [Sr.sup.2+] cannot replace [Ca.sup.2+] in facilitation of agonist-activated [Ca.sup.2+]-dependent nonselective cation channels. It is not known whether [Sr.sup.2+] can replace [Ca.sup.2+] in small G protein-mediated sensitization of phosphorylation. To explore mechanisms involved in [alpha]-receptor-activated contractions in smooth muscle, effects of replacing [Ca.sup.2+] with [Sr.sup.2+] were examined in rat portal vein. Norepinephrine (NE) at >3.0 x [10.sup.-7] M in the presence of [Ca.sup.2+] resulted in a strong sustained contraction, whereas this sustained component was absent in the presence of [Sr.sup.2+]; only the amplitude of phasic contractions increased. Pretreatment with low (~0.05 mM) free [Ca.sup.2+] followed by 2.5 mM [Sr.sup.2+] resulted in a sustained component of the NE response. In [beta]-escin-permeabilized preparations, phenylephrine in the presence of GTP or guanosine 5'-O-(3-thiotriphosphate) alone induced sensitization to [Sr.sup.2+]. In conclusion, a [Ca.sup.2+]-regulated membrane/channel process is required for the sustained component of NE responses in rat portal vein. Sensitization alone is not responsible for the sustained phase of the NE contraction. vascular smooth muscle; calcium sensitization

Research was conducted to determine whether prior exercise improves net hepatic uptake (NHGU) during a glucose load. Sampling catheters, infusion catheters and Doppler flow probes were implanted. Findings showed that prior exercise increases NHGU during a glucose load when determinants of hepatic glucose uptake are regulated because of an effect that is intrinsic to the liver. Increased glucose disposal in the postexercise state is therefore caused by an enhanced ability of both liver and muscle to take up glucose.

A study was conducted to determine if the effects of insulin delivered directly to the liver sinusoid will be influenced by the route of delivery. Two routes are examined, namely via portal vein and hepatic artery. Results revealed that both means of infusion have the same effects Insulin infused through the hepatic artery and the portal vein caused the inhibition of glucose production, which effected a change in the liver glycogenolyisis.

The perforated-patch configuration of the voltage-clamp technique was used to investigate the hypotonicity-activated chloride channels of isolated portal vein vascular smooth muscle cells from rabbits. The pharmacology of the channel was investigated using a variety of inhibitors of chloride channels elsewhere in the vascular system. Results reveal that swelling enhances the conductance across the chloride channels under investigation. The possible functions of these channels are discussed.

A perfusion circuit regulating pressure and flow to a cat liver in situ was used in the investigation of the shear-induced effects of nitric oxide on hepatic artery and portal vein vasoconstriction. Results indicate that nitric oxide suppresses the postjunctional activity of the sympathetic nerve depending on the shear stress on the blood vessel. This is consistent with other investigations that show organ-selective nitric oxide regulation of vascular tone.

Research was conducted to test whether renal sympathoinhibitory response to portal venous NaCl infusion involves an action of arginine vasopressin at the area postrema of rabbits. Hematocrit, plasma Na+, potassium concentrations and plasma osmolality were determined in both intact and APL rabbits while data values were analyzed with one-way analysis of variance for comparisons among the five NaCl doses. Results indicated that neural reflexes can be modulated by circulating hormones.

The ability of endothelin (ET)-1 to constrict the hepatic vascular resistance distribution and ETA and ETB receptors in isolated rabbit livers perfused via the portal vein was investigated. Twenty-nine rabbits were used as experimental models to determine the effects of ET-1 on liver hemodynamics, weight and bile flow as well as the effects of ET receptor antagonists on hepatic vasoconstriction response caused by ET-1. Results showed that ETA and ETB receptors indeed mediated ET-1-induced hepatic constriction in rabbit livers.

Protein kinase C (PKC) is activated by contractile agonists and its stimulation leads to changes in the activity of membrane and cytoplasmic proteins. In a study of isolated rabbit portal vein smooth muscle cells, activation of PKC caused a decline in 4-aminopyridine (4-AP)-sensitive delayed rectifier current. Initial exposure of the cells to contractile agonists had no effect on the current but chronic exposure caused a marked depression of the current. The results suggest that PKC catalyzes a novel signal transduction pathway for depressing expression of the current.

Endotoxin pretreatment increases the portal circulatory systems' contractile response to endothelin-1 (ET-1) at sinusoidal and presinusoidal levels. Rat livers injected with the bacterial endotoxin lipopolysaccharide (LPS) show increased total portal resistance and zero-flow pressures in response to ET-1. LPS decreases sinusoidal diameter, volumetric flow, and red blood cell velocity. Impairment of the hepatic microcirculation by LPS is associated with liver failure.

Extraction methods and HPLC procedures were developed for analysis of potential ruminal metabolites of dietary phenolics (reduced phenolics). Hepatic portal venous blood from wethers fed bromegrass, bermudagrass, ryegrass-wheat, and alfalfa hays also was analyzed for hippuric (HA), 3-(4-hydroxyphenyl)propionic (4OHPPA), benzoic (BA), 3-phenylpropionic (PPA), and t-cinnamic (CA) acids. Additionally, mesenteric arterial and hepatic venous blood was analyzed and, in conjunction with blood flow measurements, fluxes for portal-drained viscera (PDV) and liver were calculated. Ruminal fluid from four steers fed two levels of forage and two forage particle sizes in a Latin square design was analyzed for PPA and CA. 3-Phenylpropionic and benzoic acids were the most concentrated reduced phenolics identified in hepatic portal venous blood. Concentrations of PPA in ruminal fluid varied with ruminal disappearance of p-coumaric and ferulic acids. Additionally, hepatic portal venous concentrations of PPA were correlated (P < .05) with p-coumaric acid (r = .57) and ferulic acid (r = .67) intakes. Net release of PPA from PDV was observed, suggesting absorption of PPA from the gut. The liver removed PPA and BA with less efficiency. Given the relatively high concentrations of PPA in blood of ruminants, specific effects of this reduced phenolic on liver metabolism of ruminants should be assessed. Key Words: Portal Vein, Liver, Phenolics, Ruminants

Pressure-flow analysis of the interactions between portal vein and hepatic artery in isolated and intact porcine liver preparations reveals that a decrease in portal vein flow (Qpv) induces a rise in the hepatic artery flow (Qha) and a decrease in the slope, indicating that the modulation of hepatic arterial buffer response occurs upstream of effective back pressure. Reductions in Qha induce a decrease in the back pressure (Pback) of portal vein. Modifications in total sinusoidal flow introduce changes in Pback and modifications in Qpv change the hepatic arterial resistance.

Experimental analyses of the effects of hyperinsulinemia on very low density lipoprotein (VLDL), apolipoprotein (apo) B and VLDL triglyceride (TG) production in 11 healthy males reveal that hyperinsulinemia inhibits VLDL generation and plasma free fatty acid levels in the males. The inhibitory effect requires insulin but is independent of the pathway of insulin delivery, through the peripheral or portal vein. The decreases in VLDL-TG and VLDL-apoB are similar in the exogenous insulin and tolbutamide infusion studies, which also indicate that tolbutamide has no independent impact on the VLDL-TG and apoB production.

Exercising adrenodemedullated rats demonstrate a low pancreatic hormone response when a small amount of pyurvate is infused during low blood glucose level. Pyruvate infusion into the portal vein for glucagon and into both the portal and jugular veins for insulin lowers the response of portal pancreatic hormone concentrations to exercise.

Investigations of ATP and nucleotide diphosphate (NDP) in rabbit portal vein monitoring of ATP-sensitive K+ channels suggest that intracellular ATP, NDPs and Mg2+ regulate KATP channel states. The K+ channel openers (KCO) such as pinacidil and lemakalim open KATP channels only in the operative state. Nucleotide diphosphate such as NDPs and GDP induce channel reopening in KCO presence, which is improved by Mg2+ addition.

Metabolic inhibition of ATP synthesis by the action of 2-deoxy-D-glucose and cyanide or dinitrophenols enhances the macroscopic and single-Ca2+ activated potassium channels in isolated rabbit portal vein myocytes. The channel current is voltage-dependent and inhibited by chelation of intracelluular Ca2+ and low tetraethyl-ammonium ion, but is unaffected by 4-aminopyridine. An increase in the activity of these channels contributes to membrane hyperpolarization under conditions of hypoxia or ischemia.

Cardiac excitation-contraction coupling in the portal hypertensive rat. Am J Physiol Gastrointest Liver Physiol 279: G28-G39, 2000.-- Basal contractility and responses to [Beta]-adrenoceptor activation are compromised in hearts from rats with chronic portal vein stenosis. Here we report the effect of partial ligation of the portal vein on myocardial G protein expression, [Beta]-adrenoceptor-G protein coupling, and excitation-contraction coupling (ECC). Contractility (dT/dt) was reduced 30-50% in right and left ventricles, but the rate of relaxation (-dT/dt) was unaffected. Isoproterenol-induced positive inotropism was diminished, but there was no difference in [ED.sub.50]. The concentration-dependent increase in -dT/dt was unaffected. [G.sub.s][Alpha] and [G.sub.i][Alpha] expression, cholera toxin- and pertussis toxin-induced ADP-ribosylation, and formation of the agonist-receptor-[G.sub.s] complex were unaffected by portal vein stenosis. Of the components of ECC examined, the caffeine-sensitive sarcoplasmic reticulum [Ca.sup.2+] pool was reduced 35%, although the [Ca.sup.2+] uptake and release processes were unchanged; the apparent density of L-type [Ca.sup.2+] channels decreased 60% with no change in affinity; the dihydropyridine [Ca.sup.2+] channel agonist BAY K 8644 produced relative changes in dT/dt that were similar in both groups, suggesting normal function in the remaining [Ca.sup.2+] channels; and [Na.sup.+]/[Ca.sup.2+] exchange was reduced 50% in the portal vein stenosis group. These data suggest that the effect of portal vein stenosis on the myocardium is the result of alterations to ECC. isradipine; BAY K 8644; portal hypertension; [Beta]-adrenoceptor; isoproterenol; G protein; heart; sarcoplasmic reticulum; sodium/calcium exchange

We hypothesized that there is no synthesis of butyric acid within organs or tissues not drained by the portal vein (PV). Two experiments were performed. In six piglets, the colonic vasculature was clamped (n = 4) or the entire colon resected while [1-[sup.13]C]-butyric acid (99% enriched) was infused into a jejunal vein for 120 min; [sup.13]C enrichment of butyric acid was measured in the PV and carotid artery (ART) during the last 30 min of the infusion. In a second experiment, butyric acid tracer and unlabeled disaccharide were infused into the cecum for 120 min, and blood again was sampled from the PV and ART. For the four piglets studied during ligation of the colonic vasculature, the mean ([+ or -] SD) ratio of the butyric acid enrichment in the ART to that in the PV (ART/PV) was 0.80 [+ or -] 0.05 (ART vs. PV, P = 0.002) and for all six piglets in expt. 1, the ART/PV ratio was 0.74 [+ or -] 0.1 (ART vs. PV, P = 0.001). The enrichment of butyric acid in the PV averaged 96.0% for the six studies, implying that splanchnic tissues other than the colon did not produce a substantial amount of butyric acid. For the second experiment, the ART/PV ratio was 0.80 [+ or -] 0.15 (ART vs. PV, P = 0.03). These studies provide the first evidence for endogenous synthesis of butyric acid by piglets. J. Nutr. 130: 234-237, 2000. KEY WORDS: * butyric acid * endogenous synthesis * fermentation * Sus scrofa * swine