The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6-hydroxydopamine (6-OHDA) causes selective acute degeneration of the adrenergic nerve terminals--that is, a reversible chemical sympathectomy. The effect of this drug was studied on the insulin-stimulated gastric secretion. Insulin-stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after 6-OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibers in the vagus nerve might have some modulating effect on the insulin-induced gastrin release.

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6 hydroxydopamine (6 OHDA) causes selective acute degeneration of the adrenergic nerve terminals, that is a reversible chemical sympathectomy. The effect of this drug was studied on the insulin stimulated gastric secretion. Insulin stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin was measured before and after 6 OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations, that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibres in the vagus nerve might have some moduling effect on the insulin induced gastrin release.

The effect of propranolol on insulin-stimulated gastric secretion in dogs.

The effect of beta-adrenergic blockade on the insulin hypoglycemia-induced gastric secretion was studied. Insulin-stimulated (0.15 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after beta-adrenergic blockade with propranolol (20 microgram/kg/min intravenous infusion) in gastric fistula and Heidenhain pouch dogs. Insulin injection caused acid and pepsin secretion from the gastric fistula, and both acid and pepsin secretion was significantly increased during beta-adrenergic blockade. Significant gastrin release was observed after insulin stimulation. However, the insulin-induced gastrin release was unaltered by intravenous infusion of propranolol. The Heidenhain pouch did not show any secretion in these experiments. It is concluded that beta-adrenergic blockade augments the hypoglycemia-induced gastric secretion in dogs. Furthermore, it seems that this effect is not dependent on vagally released gastrin.

Non-gastrin, intestinal-phase secretion. Experimental confirmation in the dog.

Four mongrel dogs were prepared with a Heidenhain pouch, a gastric fistula, and a 90-cm-long Thiry-Vella loop. After recovery, dose-response curves were obtained with different doses of pentagastrin, and the maximal acid output was determined. The jejunal loop was perfused for 3 h with either 5% liver extract or with 0.15 M NaCl at a rate of 114 ml/h. To verify that the stomach could release gastrin and that the assay could detect that change, antral perfusion with liver extract was performed. Serum gastrin levels and acid output were measured every 30 min. Perfusion of the jejunal loop with liver extract resulted in a significant increase in acid output from the Heidenhain pouch and the gastric fistula, whereas perfusion with saline solution failed to show any changes. The magnitude of acid response from the Heidenhain pouch and gastric fistula was 11% and 18%, respectively, as compared with maximal pentagastrin stimulation. The serum gastrin levels remained unchanged during both liver extract and saline perfusion of the jejunal loop, in contrast to the marked increase in serum gastrin level after antral perfusion. The results confirm the existence of the intestinal phase of gastric acid stimulation in dogs as an entity and show that the magnitude of this phase is significantly lower than has been suggested by results of earlier studies. Furthermore, the results suggest that the intestinal phase of gastric secretion in dogs is most probably elicited through a humoral agent other than gastrin.

Role of the sympathetic nervous system in peptic ulcer production in rats.

The role of the sympathetic nervous system in gastric acid secretion and in experimental duodenal ulceration (cysteamine induced) was studied in rats. The animals were divided randomly into seven groups: (1) control, (2) sham-operated, (3) surgical sympathectomy, (4) chemical sympathectomy (6-HODA), (5) vagotomy, (6) surgical sympathectomy plus vagotomy, and (7) chemical sympathectomy plus vagotomy. Results on gastric acid secretion were expressed as gastric acid output (GAO = micronEq of acid secretion in 1 hour). The means in the control and sham groups were 447.83 +/- 26.67 GAO and 399 +/- 36.4 GAO, respectively. The means in the sympathectomized rats (surgically = 562 +/- 27.21 GAO and chemically = 648.66 +/- 46.53 GAO) were higher (P less than 0.01) than those of the control and sham groups. In the vagotomized group the mean was 156.6 +/- 17.64 GAO, lower than those of the control and sham groups (P less than 0.001). The incidence of ulceration was 47.5% and 46% in the control and sham groups, respectively. Both the sympathectomized groups (surgically, 73%; chemically, 77%), had a significantly elevated incidence of ulceration as compared with the controls (P less than 0.01). The vagotomized group had a 14% incidence of ulceration. These results clearly indicate that sympathectomy has a definite effect on gastric acid secretion and on the incidence of experimental peptic ulceration in rats.

An electron microscopic study of the distribution of sodium in normal, pentagastrin-stimulated and secretin-inhibited fundic mucosa of the stomach of the rat.

Normal, pentagastrin-stimulated and secretin-inhibited stomachs of rats were fixed either by perfusion or by immersion in an unbuffered osmium tetroxide potassium pyroantimonate mixture at a pH of 7.6, and the mucosa from the fundic area was examined under the electron microscope for sodium localization. Both fixation methods gave comparable results. In the control tissue, sodium pyroantimonate crystals were mainly seen in and around the collagen fibers in the interstitium and to a lesser extent in the basal and lateral plasma membranes of the epithelial cells. No significant differences were noticed in the secretin-inhibited tissue. In contrast, in the pentagastrin-stimulated mucosa, an increase in the amount of precipitate along with a redistribution occurred. The pyroantimonate technique seems promising for studying the mechanism of sodium transport in the gastric mucosa.

Neural control of blood flow in gastric mucosa.

The innervation of the small vessels in the fundic mucosa of the rat and the effects of vagotomy on this innervation were studied ultrastructurally. The capillaries and arterioles, but not the venules, were found to receive direct innervation. Vagotomy causes degeneration of the nerve endings that innervate these vessels, confirming their vagal origin. This finding, and the fact that some morphologic changes in the capillaries were observed after vagotomy, provides morphologic evidence for the neural control of blood flow in the rodent gastric mucosa.

Effects of vagotomy on the catecholamine-containing cells in the gastric mucosa of the rat: an electron microscopic study.

The ECL cells in the fundic mucosa from five different groups of fasted rats were examined by means of electron microscopy; in the control animals, the majority of the secretory granule of the ECL cells contained electron-dense material. Previous studies in our laboratory indicate that this material probably represents a catecholamine. In the second and third groups, in which truncal vagotomy plus pyloroplasty was performed, the secretory granules were depleted of their content. In the fourth group in which vagotomized animals were treated with iproniazid and L-dopa, the mature secretory granules were depleted but formation of new granules was apparent. In the fifth group, in which pyloroplasty alone had been performed, the content of the granules was the same as in the control group. It was concluded that the endocrine function of the ECL cells is under vagal control and that vagotomy causes release of catecholamines from these cells.