Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

Abstract

In rats, ventromedial hypothalamic (VMH) lesions induce cell proliferation in the visceral organs (stomach, small intestine, liver, and pancreas) due to hyperactivity of the vagus nerve. To investigate the effects of selective gastric vagotomy on VMH lesion-induced cell proliferation and secretion of gastric acid, we assessed the mitotic index (the number of proliferating cell nuclear antigen (PCNA)-immunopositive cells per 1,000 cells in the gastric mucosal cell layer) and measured the volume of secreted basal gastric acid. Furthermore, to explore whether or not ethanol-induced acute gastric mucosal lesions (AGML) lead to ulcer formation in VMH-lesioned rats, we assessed the ulcer index of both sham-operated and VMH-lesioned rats after administration of ethanol. VMH lesions resulted in an increased mitotic index and thickness of the gastric mucosal cell layer and gave rise to the hypersecretion of gastric acid. Selective gastric vagotomy restored these parameters to normal without affecting cell proliferation in other visceral organs. Ethanol-induced AGML caused ulcers in sham VMH-lesioned rats, whereas VMH-lesioned rats were less likely to exhibit such ulcers. These results suggest that VMH lesion-induced vagally mediated cell proliferation in the visceral organs is associated with hyperfunction in these organs, and VMH lesion-induced resistance to ethanol may be due to thickening of the gastric mucosal cell layer resulting from cell proliferation in the gastric mucosa-this in turn is due to hyperactivity of the vagus nerve.

Cell proliferation in visceral organs induced by ventromedial hypothalamic (VMH) lesions: Development of electrical VMH lesions in mice and resulting pathophysiological profiles

“…Furthermore, the thickness of the jejunal mucosa of the small intestine, which resulted from cell proliferation in the small intestine, was significantly enlarged in VMH-lesioned mice. These results correspond to the cell proliferation in the visceral organs induced in electrical VMHlesioned rats, as previously observed by increased [ 3 H] thymidine incorporation [12][13][14] and increased positive cell numbers with PCNA staining [19] in these rats. Therefore, VMH-lesioned mice appear to be an appropriate model for identifying genes for proliferative or regenerative factors in VMH-lesioned animals [12][13][14][15].…”

“…In VMH-lesioned rats, there is an initial period of rapid weight gain with marked hyperphagia for 4-5 weeks after VMH-lesioning (dynamic phase), followed by a slowing period when weight gain is very mild with previous study [19] and in VMH-lesioned mice in the present study. Furthermore, we found selective proliferation of β-cells in pancreatic Langerhans islet cells in VMH-lesioned rats in a previous study [14], and thus we hope to identify factors that induce specific proliferation of pancreatic β-cells through vagal activation by VMH lesions using this developed model.…”

“…hypergastric acid secretion in VMH-lesioned rats [19]. This suggests that cell proliferation in visceral organs in VMH-lesioned animals is associated with enhanced function of the visceral organs.…”

“…We believe that cell proliferation of liver and pancreas in VMH-lesioned animal originates, at least in part, from self-replication since the increased [ 3 H] thymidine uptake [12,14] and increased PCNA positive staining [19] in these organs in our previous studies suggested enhanced nuclear division of these cells. Therefore, it is of interest to identify growth factors related to cell proliferation and/or regeneration of the visceral organs induced by hyperactivity of the vagus nerve after formation of VMH lesions [12][13][14] for searching for an another approach to pancreas and liver regeneration.…”

Esophageal motility, vagal function and gastroesophageal reflux in a cohort of adult asthmatics

“…Increased vagal stimulation increases rate and amount of acid secretion and could therefore augment the damaging effects of GER in these subjects [49]. Acid also inhibits the vagal low threshold mechano-sensors in the esophagus that are responsible for the reflex regulation of esophageal motor functions.…”