Role of ethanol metabolism in the ethanol-induced increase in splanchnic circulation

1986 ◽  
Vol 250 (4) ◽  
pp. G518-G523 ◽  
Author(s):  
J. P. McKaigney ◽  
F. J. Carmichael ◽  
V. Saldivia ◽  
Y. Israel ◽  
H. Orrego
Keyword(s):  
Blood Flow ◽  
Liver Blood Flow ◽  
Portal Blood Flow ◽  
Splanchnic Blood Flow ◽  
Ethanol Metabolism ◽  
Radioactive Microsphere ◽  
Splanchnic Hemodynamics ◽  
Radioactive Microsphere Technique ◽  
Blood Flow Increase

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.

Role of EDRF in splanchnic blood flow of normal and chronic portal hypertensive rats

1992 ◽  
Vol 263 (2) ◽  
pp. G149-G154 ◽  
Author(s):  
F. Iwata ◽  
T. Joh ◽  
T. Kawai ◽  
M. Itoh
Keyword(s):  
Blood Flow ◽  
Splanchnic Blood Flow ◽  
Constant Infusion ◽  
Relaxing Factor ◽  
Radioactive Microsphere ◽  
Blood Flow Reduction ◽  
Microsphere Method ◽  
Radioactive Microsphere Method ◽  
Endothelium Derived Relaxing Factor

The role of endogenous endothelium-derived relaxing factor (EDRF) in splanchnic blood flow was assessed in normal and portal vein-stenosed rats (PSRs). Specific and maximal inhibition of EDRF was achieved by intravenous administration of NG-nitro-L-arginine (L-NOARG) as a 1.75 mumol/kg bolus, followed by constant infusion of 1.75 mumol/kg for 20 min. Pretreatment with L-arginine (175 mumol/kg iv) completely blocked both hypertension and the reduction in blood flow induced by L-NOARG. Pretreatment with D-arginine (175 mumol/kg iv) and prazosin (500 micrograms/kg iv) did not attenuate the pressor effect of L-NOARG. These results indicate that L-NOARG selectively blocks EDRF. The blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats was 81.1 +/- 8.7, 199.1 +/- 21.9, 153.3 +/- 20.0, 68.6 +/- 10.6, 79.4 +/- 11.8, and 59.3 +/- 7.8 ml.min-1.100 g-1, respectively, and in PSRs was 141.4 +/- 10.8, 244.0 +/- 10.4, 208.3 +/- 9.8, 126.8 +/- 13.0, 166.9 +/- 16.5, and 94.8 +/- 4.7 ml.min-1.100 g-1, respectively. Blood flow was measured using the radioactive microsphere method. L-NOARG significantly reduced blood flow to the stomach, duodenum, jejunum, ileum, cecum, and colon in control rats by 47, 44, 48, 55, 40, and 41%, respectively, and in PSRs by 30, 27, 36, 33, 28, and 23%, respectively. The magnitude of blood flow reduction in PSRs was lower than in normal rats. These results indicate that EDRF plays an important role in control of the splanchnic circulation, but its effect on the hyperdynamic circulation observed in PSRs is insignificant.

Systemic and regional haemodynamic effects of a synthetic atrial natriuretic peptide in conscious rats

1986 ◽  
Vol 71 (3) ◽  
pp. 323-325 ◽  
Author(s):  
Carlos Caramelo ◽  
Arturo Fernandez-Cruz ◽  
Luis M. Villamediana ◽  
Elias Sanz ◽  
Diego Rodriguez-Puyol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Portal Blood Flow ◽  
Haemodynamic Effects ◽  
Conscious Rats ◽  
Blood Flows ◽  
Radioactive Microsphere ◽  
Radioactive Microsphere Technique ◽  
Atrial Natriuretic

1. The effect of the intravenous injection of synthetic atrial natriuretic peptide (ANP, 2 μg) on systemic haemodynamics and blood flow to several organs has been studied in conscious rats by the radioactive microsphere technique. 2. ANP induced a 540% increase in sodium excretion and a 310% increase in urine flow. Mean arterial pressure decreased by 21 mmHg and the peripheral resistances decreased by 26%, without significant changes in cardiac output. 3. Renal blood flow increased by 37.7% and small intestine and portal blood flow increased by 39% and by 28% respectively. No other alterations in organ blood flows were observed. 4. From these data it can be concluded that atrial natriuretic peptide shows acute vascular relaxant properties, which seem to be specific for renal and mesenteric territories.

Splanchnic blood flow, O2 consumption, removal of lactate, and output of glucose in highlanders

1977 ◽  
Vol 43 (2) ◽  
pp. 204-210 ◽  
Author(s):  
A. Capderou ◽  
J. Polianski ◽  
J. Mensch-Dechene ◽  
L. Drouet ◽  
G. Antezana ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Splanchnic Blood Flow ◽  
O2 Consumption ◽  
Arterial Lactate ◽  
Oxygen Breathing ◽  
Arterial Blood ◽  
Splanchnic Hemodynamics ◽  
Arterial Blood Glucose ◽  
Arteriovenous Difference

An impairment of gluconeogenesis has been proposed to explain the low arterial blood glucose of highlanders. Therefore, we studied splanchnic blood flow, splanchnic uptake of oxygen and lactate, and output of glucose in nine normal and six anemic highlanders at an altitude of 3,750 m. Splanchnic blood flow, arteriovenous difference for oxygen, and oxygen consumption were comparable at rest in both groups and in lowlanders from the literature, whereas splanchnic output of glucose, and uptake of lactate were approximately twice those in lowlanders. After 10 min of mild exercise in 12 subjects (7 normals, 5 anemic), no significant changes in splanchnic hemodynamics and metabolism were found. During 29% oxygen breathing in 8 subjects (5 normals, 3 anemics), arterial lactate, splanchnic uptake of lactate and output of glucose fell to normal sea-level values. We concluded that splanchnic hemodynamics are similar in adapted highlanders and in lowlanders, and that there is no evidence of an impaired gluconeogenesis at the altitude of the present study.

Fluorescent microspheres are superior to radioactive microspheres in chronic blood flow measurements

1998 ◽  
Vol 275 (1) ◽  
pp. H110-H115 ◽  
Author(s):  
Matthijs F. M. Van Oosterhout ◽  
Frits W. Prinzen ◽  
S. Sakurada ◽  
Robb W. Glenny ◽  
J. Robert S. Hales
Keyword(s):  
Blood Flow ◽  
Liver Blood Flow ◽  
Mean Difference ◽  
Radioactive Microspheres ◽  
Fluorescent Microspheres ◽  
Flow Measurements ◽  
Change Over Time ◽  
Radioactive Microsphere ◽  
Blood Flow Measurements ◽  
Over Time

The accuracy of the fluorescent (FM) and radioactive microsphere (RM) techniques is similar in acute experiments but has not been established in chronic experiments. In the present study various combinations (at least pairs) of FM and/or RM labels were injected simultaneously between 2 mo and 5 min before each animal was killed. Blood flow was determined in many organs. Intramethod mean difference and variation did not change over time for FM but increased significantly for RM (from 1.8 ± 1.4 to 25.6 ± 21.8% and from 4.4 ± 3.2 to 32.4 ± 23.0% at 5 min and 2 mo, respectively). Also the FM-RM intermethod mean difference and variation increased (from −0.5 ± 8.5 to 40.8 ± 23.8% and from 23.6 ± 4.6 to 71.8 ± 34.3%, respectively). After 2 mo, blood flow estimations were 20–50% lower with the various RM, whereas brain and liver blood flow values varied even more between isotopes. Underestimation started within 1 day for51Cr and within 2 wk for141Ce,95Nb, and85Sr. We conclude that FM are superior to RM for blood flow determination in experiments lasting longer than 1 day, presumably because of leaching of isotopes from RM.

scholarly journals Validation of Pharmacological Protocols for Targeted Inhibition of Canalicular MRP2 Activity in Hepatocytes Using [99mTc]mebrofenin Imaging in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 486
Author(s):  
Solène Marie ◽  
Irene Hernández-Lozano ◽  
Louise Breuil ◽  
Wadad Saba ◽  
Anthony Novell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Biliary Excretion ◽  
Low Dose ◽  
Organic Anion ◽  
Liver Blood Flow ◽  
High Dose ◽  
Liver Uptake ◽  
Targeted Inhibition ◽  
Substrate Inhibitor

The multidrug resistance-associated protein 2 (MRP2) mediates the biliary excretion of drugs and metabolites. [99mTc]mebrofenin may be employed as a probe for hepatic MRP2 activity because its biliary excretion is predominantly mediated by this transporter. As the liver uptake of [99mTc]mebrofenin depends on organic anion-transporting polypeptide (OATP) activity, a safe protocol for targeted inhibition of hepatic MRP2 is needed to study the intrinsic role of each transporter system. Diltiazem (DTZ) and cyclosporin A (CsA) were first confirmed to be potent MRP2 inhibitors in vitro. Dynamic acquisitions were performed in rats (n = 5–6 per group) to assess the kinetics of [99mTc]mebrofenin in the liver, intestine and heart-blood pool after increasing doses of inhibitors. Their impact on hepatic blood flow was assessed using Doppler ultrasound (n = 4). DTZ (s.c., 10 mg/kg) and low-dose CsA (i.v., 0.01 mg/kg) selectively decreased the transfer of [99mTc]mebrofenin from the liver to the bile (k3). Higher doses of DTZ and CsA did not further decrease k3 but dose-dependently decreased the uptake (k1) and backflux (k2) rate constants between blood and liver. High dose of DTZ (i.v., 3 mg/kg) but not CsA (i.v., 5 mg/kg) significantly decreased the blood flow in the portal vein and hepatic artery. Targeted pharmacological inhibition of hepatic MRP2 activity can be achieved in vivo without impacting OATP activity and liver blood flow. Clinical studies are warranted to validate [99mTc]mebrofenin in combination with low-dose CsA as a novel substrate/inhibitor pair to untangle the role of OATP and MRP2 activity in liver diseases.

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renin Angiotensin System ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Control Group ◽  
Moderate Exercise ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

scholarly journals The use of vasoconstrictors in patients with liver cirrhosis: how, when, why

2012 ◽  
Vol 6 (3) ◽  
pp. 105-115
Author(s):  
Claudio Puoti
Keyword(s):  
Blood Flow ◽  
Liver Cirrhosis ◽  
Hepatorenal Syndrome ◽  
Portal Blood Flow ◽  
Decompensated Cirrhosis ◽  
Enos Activity ◽  
Enhanced Production ◽  
Massive Gastrointestinal Bleeding ◽  
No Release

Portal hypertension (PH) is a severe complication of liver cirrhosis. Patients with PH run the risk of developing gastro-esophageal varices and massive gastrointestinal bleeding, ascites, hepatorenal syndrome, and hepatic encephalopathy. Portal blood flow in its turn increases because of enhanced production of vasodilators, increased eNOS activity and NO release, systemic and splanchnic vasodilation, hyperkinetic circulation, and hyposensitivity to vasoconstrictors. Thus, it is now widely recognized that this hyperkinetic (hyperdynamic) circulation that characterizes liver cirrhosis is the main cause of the complications of the disease. This review is aimed at addressing the role of vasoconstrictor treatment in patients suffering from complications of decompensated cirrhosis, offering practical suggestions for the management of this treatment at bedside. In particular, the management of terlipressin in patients with cirrhosis, its side effects and the efficacy of this vasoconstrictor will be examined.

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