Takeo Sakaguchi

HEPATIC BRANCH VAGOTOMY CAN SUPPRESS LIVER REGENERATION IN PARTIALLY HEPATECTOMIZED RATS

The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy. These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically.

Inhibition of gastric motility induced by activation of the hypothalamic paraventricular nucleus

Electrical stimulation of the paraventricular nucleus depressed the intragastric pressure of adrenalectomized male rats of which gastric movement had been induced by insulin-hypoglycemia. Electrical stimulation to the pituitary stalk produced a similar response in the pressure, but the response was abolished by bilateral lesion of the paraventricular nucleus. These findings allow us to speculate that the paraventricular nucleus is capable of modulating gastric motility, and suggest that the nucleus has a neural connection between the neurohypophysis and the system relevant to visceral function.

Alterations in gastric acid secretion following hepatic portal injections of d-glucose and its anomers

Changes in acid outputs from the stomach were examined after portal injections of D-glucose and its optical anomers in the bilaterally adrenalectomized rats with insulin hypoglycaemia. Significant decrease in gastric acid outputs was noted after portal injections of alpha-D-glucose, optically equilibrated D-glucose (OEDG) consisting of 36% alpha-anomer and 64% beta-anomer and beta-D-glucose. The effect of beta-D-glucose was most potent in reducing the acid outputs and the inhibitory response was entirely prevented by prior vagotomy at the hepatic level. The injections of isotonic NaCl solution, however, produced no change in the acid outputs. Results suggest that changes in glucose levels in the portal vein may modulate gastric acid secretion through hepatic vagal afferents and gastric vagal efferents and suggest that activation of hepatic glucosensitive mechanisms may be dependent on the anomeric stereospecificity of D-glucose in the blood.

Liver regeneration enhanced by orally administered ursodesoxycholic acid is mediated by immunosuppression in partially hepatectomized rats

The relationship of liver regeneration to immunoactivity was examined after ursodesoxycholic acid (UDCA) administration to partially (about 66%) hepatectomized rats. The UDCA was given orally. Liver regeneration was evaluated by the hepatocyte mitotic index (MI) and immunoactivity by natural killer cell (NK) activity in the blood. When UDCA 12.5 mg/kg/day was administered, a significant increase in the MI was observed 2 and 3 days after hepatectomy, and the MI response 2 days after bepatectomy tended to be dose-dependent in the range of 0-25 mg/kg/day. NK activity was decreased 2 days after hepatectomy when UDCA was given, and a significant correlation between MI and NK activity was obtained. The increase in MI and decrease in NK activity was blocked completely or partially (respectively) by interleukin-2 administration. It was also noted that UDCA did not affect serum parameters indicating liver and kidney function. These findings suggest that liver regeneration can be modified by orally administered UDCA through a change in immunoactivity.

A pharmacological analysis of prostaglandin E1 on portal blood flow after partial hepatectomy in rats.

Portal venous flow (PVF) and portal venous pressure (PVP) were examined after the jugular or portal injection of Prostaglandin E1 (PGE) in rats partially hepatectomized by either 40% or 66%. In the 66% hepatectomized animals, the jugular injection of PGE at 5.0 μg/kg/min produced an increase in PVF concomitant with a fall in systemic arterial pressure (SAP), while PVP remained unchanged. The portal injection of PGE at 0.5 μg/kg/min increased PVF to a level equivalent to that evoked by the jugular injection of 5.0 μg/kg/min PGE, without any change in SAP. PVP was reduced synchronistically with an increase in PVF. The PVF response to a portal injection of PGE at 0.5 μg/kg/min was not reproduced in liver intact rats. These results suggest that PGE is potent in increasing PVF in the partially resected condition of the liver and that the portal vascular bed is involved in this response.

Prostaglandin E1 enhances hepatic portal venous flow by dilating the portal vascular bed in 70% hepatectomized dog

SummaryThe effects of portal, hepatic arterial and femoral venous administration of prostaglandin E1 (PGE) on portal venous flow (PVF) and hepatic arterial flow HAF were examined before and after 70% hepatectomy in anesthetized dogs. In the hepatectomized condition, portal venous administration of PGE (0.5 μ/kg/min) caused an increase in PVF without any change in systemic arterial pressure (SAP). HAF was unchanged following the injection. The portal effect of PGE on PVF was dose-dependent, and a reduction in portal venous resistance was seen. However, the same dose of PGE failed to change PVF under intact liver conditions. Hepatic arterial administration of PGE (0.5 μ/kg/min) brought no significant change in PVF or HAF, with or without hepatectomy. Femoral venous administration of PGE (0.5μ/kg/min) produced an increase in PVF concomitant with a significant decrease in SAP. HAF showed no change after the injection. A decrease in PVR was seen only in the hepatectomized condition. It is concluded that PGE is potent in increasing PVF in the hepatectomized condition, and the portal vasculature is involved as the site of action.

Pancreatic vagal functional distribution in the secretion of insulin evoked by portal infusion of D-glucose.

The vagus glucose signal pathway relevant to hepatic portal control of insulin secretion was examined in bilaterally adrenalectomized rats. The increase in the insulin concentration after portal glucose injection was completely blocked by vagotomy of the hepatic branch which is bifurcated from the ventral vagus trunk at the subdiaphragmatic level. At the cervical level, the reduction in the insulin concentration showed no laterality following vagotomy on either side. The insulin response was mainly suppressed by prior section of the branch of the ventral vagus trunk at the celiac level. These results suggest that the hepatic glucose signal evoking insulin release has a specific pathway from the liver to the pancreas, and that there is functional laterality in this pathway in the visceral cavity.

Orally Administered Ginseng Extract Reduces Serum Total Cholesterol and Triglycerides That Induce Fatty Liver in 66% Hepatectomized Rats:

The effects of ginseng extract (from the root of Panax ginseng) on factors inducing fatty liver were examined in 66% hepatectomized rats. Oral administration of ginseng extract at 125 or 250 mg/kg/day produced statistically significant reductions in total cholesterol and triglyceride concentrations in the blood 3 days after hepatectomy (P < 0.05); the total cholesterol response appeared to be dose-related. Administration of ginseng extract at both doses also reduced total cholesterol and triglyceride concentrations in the liver 3 days after hepatectomy. Food intake and serum chemistry parameters indicating liver and kidney function were unchanged after ginseng administration except for the lipid metabolic parameters. These observations suggest that orally administered ginseng extract can suppress the formation of fatty liver after hepatic resection.

Orally administered Panax ginseng extract decreases platelet adhesiveness in 66% hepatectomized rats

The effect of oral administration of Panax ginseng extract (GE) on platelet adhesiveness was examined in 66% hepatectomized rats. A significant decrease in platelet adhesiveness was obtained when 125 mg/kg/day GE was administered for 6 days before and after hepatectomy. The total cholesterol concentration in the serum was also decreased by GE administration. Food intake was unaffected by GE administration. Serum parameters indicating liver and kidney function were unchanged after GE administration except for lipid metabolic parameters. Because enhanced platelet adhesiveness and hyperlipidemia induces atherosclerosis, these results suggest that orally administered GE is capable of improving the atherosclerotic condition associated with hepatectomy.

The effect of electrical stimulation of the hepatic branch of the vagus nerve on the secretion of gastric acid in the rat

Abstract Electrical stimulation of the hepatic vagus nerve brought a transient increase in acid concentration in a perfusate collected from the stomach. These observations suggest that there might be a neural system which modulates the secretion of gastric acid through hepatic vagal afferents and gastric vagal efferents.