Nervous control of pancreatic endocrine secretion in pigs. V. Influence of the sympathetic nervous system on the pancreatic secretion of insulin and glucagon, and on the insulin and glucagon response to vagal stimulation

Electrical stimulation of the splanchnic nerves in anesthetized pigs was found to stimulate markedly the pancreatic secretion of glucagon. The response pattern was glucose dependent, the glucagon responses at blood glucose concentrations below 4.5 mmol x l-1 being significantly greater than those noted during stimulation at higher concentrations. Insulin secretion was stimulated weakly and variably and only at higher glucose levels. The magnitude of the glucagon response was comparable to that obtained by electrical stimulation of the thoracic vagus nerves with the same frequency. The glucagon response to combined vagal and splanchnic stimulation was nearly identical to the sum of the responses to the two types of stimulation, whereas splanchnic stimulation abolished or reduced the increase in insulin secretion elicited by vagal stimulation. Combined alpha- and beta-adrenergic blockade markedly reduced the glucagon responses to splanchnic stimulation.     

Nervous control of pancreatic endocrine secretion in pigs

The increases in the concentrations of insulin and pancreatic glucagon in portal venous and arterial plasma in response to electrical stimulation of the vagus nerves were studied in anesthetized splanchnicotomized young pigs. The responses were frequence dependent; threshold frequency was below 1 Hz and maximum response was reached at 8–12 Hz. With maximal stimulation responses of magnitudes comparable to the responses to maximal arginine (glucagon) and glucose stimulation (insulin) were observed. However, both the insulin and the glucagon response were critically dependent on the blood glucose concentration during the stimulation: the glucagon response was inversely correlated to blood glucose, whereas the insulin response was positively correlated to blood glucose at concentrations above 4.5 mmol · 1^-1. Below this glucose concentration there was no detectable insulin response and above 8.0 mmol ·^-1 no glucagon response to vagal stimulation. A stimulated secretion of glucagon as well as insulin was maintained for up to 30 min stimulation, but insulin secretion tended to decrease, whereas glucagon secretion tended to increase. Above blood glucose concentrations of 4 mmol · 1^-1, blood glucose concentrations increased slightly in response to vagal stimulation, whereas no change was noted during stimulations performed at lower blood glucose concentrations.     

Nervous control of pancreatic endocrine secretion in pigs IV. The effect of somatostatin on the insulin and glucagon responses to electrical vagal stimulation and to intraarterial acetylcholine

We studied the effect of a primed i.v. infusion of somatostatin (0.5 μg×min^–1×kg^–1 on the glucose dependent insulin and glucagon responses to electrical stimulation of the vagus nerves or to i.a. acetylcholine in anesthetized pigs. Somatostatin completely abolished the insulin and glucagon responses to ongoing vagal stimulation; after 70 min somatostatin infusion the response to reiterated stimulation was profoundly inhibited. After termination of the somatostatin infusion, a considerable rebound secretion of insulin and glucagon was noted. By contrast, the endocrine response to acetylcholine persisted in spite of the somatostatin administration. Blood glucose increased slightly during somatostatin infusion. The results suggest that somatostatin inhibits the responses to vagal stimulation by interference with the neural transmission to the pancreatic islets rather than by inhibition of the islet cells themselves; acetylcholine may be involved in this neural transmission (acting on nicotinic receptors.     

Effects of adrenergic blockade on the release of insulin,glucagon and somatostatin from the pancreas in response to splanchnic nerve stimulation in cats

The effects of α-,β- or α+β-adrenergic blockade on arterial plasma concentrations of insulin, glucagon and somatostatin in response to splanchnic nerve stimulation were studied in anesthetized cats. In control experiments splanchnic nerve stimulation caused a marked rise in plasma glucose and glucagon concentrations and a marked fall in insulin but somatostatin was unaffected. Pretreatment with phentolamine significantly increased basal plasma insulin concentration but the response pattern to splanchnic nerve stimulation was not altered. Propranolol attenuated both the glucose and insulin responses. Combined α-and β-blockade abolished the hyperglycemia and hypoinsulinemia induced by splanchnic nerve stimulation, whereas the rise in plasma glucagon was not affected. It is concluded that insulin release from the pancreas and glucose release from the liver is controlled by adrenergic mechanisms whereas pancreatic glucagon and somatostatin secretion is relatively insensitive to splanchnic nerve stimulation in cats.     

Nervous control of pancreatic endocrine secretion in pigs. III. The effect of acetylcholine on the pancreatic secretion of insulin and glucagon

We studied the effect of intraarterial administration of acetylcholine on insulin and glucagon secretion in anesthetized splanchnicotomized pigs and on insulin, glucagon, and pancreatic polypeptide secretion from the isolated perfused porcine pancreas and the isolated perfused duodeno-pancreatic block of pigs and dogs. In the pigs acetylcholine stimulated insulin and glucagon secretion in a glucose dependent manner similar to vagal stimulation; however, the response was completely resistant to hexamethonium and abolished by atropine. Acetylcholine stimulated insulin and pancreatic polypeptide secretion of the isolated perfused porcine pancreas, and inhibited glucagon secretion, whether the duodenum was present or not, whereas the glucagon secretion of the isolated perfused canine pancreas was stimulated by acetylcholine.     

The release of pancreatic glucagon and inhibition of insulin in response to stimulation of the sympathetic innervation.

The changes in the concentration of glucagon and insulin in arterial plasma which occur in response to splanchnic nerve stimulation have been investigated in adrenalectomized dogs, cats and sheep. 2. In dogs, stimulation of both splanchnic nerves at a low frequency (2-0 c/s) for 10 min produced a small but statistically significant increase in plasma glucagon concentration and appeared to inhibit the release of insulin. Stimulation at a higher frequency (10-0 c/s) produced a much greater increase in plasma glucagon concentration, which was normally accompanied by a rise in plasma glucose concentration. 3. Qualitatively similar changes in plasma glucagon and insulin concentration were observed in both sheep and cats in response to adrenergic stimulation. 4. Intramesenteric infusions of glucagon at a dose of 5-0 ng kg-1 min-1 in dogs produced a comparable rise in plasma glucagon concentration to that elicited by splanchnic nerve stimulation at high frequency (10-0 c/s) and invariably caused a rise in plasma glucose concentration. 5. In dogs given exogenous glucose, release of glucagon in response to splanchnic nerve stimulation was unaffected by induced hyperglycaemia. Secretion of insulin was partially inhibited by stimulation at 2-0 c/s and completely suppressed at higher frequency (10-0c/s). 6. It is concluded that stimulation of the sympathetic innervation to the pancreatic islets, at frequencies within thephysiological range, stimulates the release of glucagon and inhibits that of insulin in each of these species.     

Nervous control of pancreatic exocrine secretion in pigs

The pancreatic secretion of fluid, bicarbonate and protein in response to electrical stimulation of the vagus and splanchnic nerves, to exogenous and endogenous secretin and to various pharmacological agents was studied in anesthetized young pigs (21 kg). Vagal stimulation increased flow, bicarbonate output and protein output in a frequency dependent manner; the half maximal effective frequency was 2–4 Hz and the maximal effective frequency 12 Hz. The secretory response to vagal stimulation was potentiated by physiological elevations of the arterial concentration of secretin brought about by injection of secretin or by acidification of the duodenal bulb. Simultaneous stimulation of the splanchnic nerves strongly inhibited the response to vagal stimulation; splanchnic nerve stimulation alone had no demonstrable effect. The flow and bicarbonate response to vagal stimulation was unaffected by atropine, but abolished by hexa-methonium. Protein output was strongly inhibited by both agents. The response to intraarterial infusion of acetylcholine resembled that elicited by vagal stimulation but it was smaller and it was completely abolished by atropine and unaffected by hexamethonium. Alpha- and beta-adrenergic blockade stimulated rather than inhibited the secretory response to vagal stimulation. The portal vein plasma concentration of secretin was not affected by vagal stimulation. The results indicate that the protein response, and the flow and bicarbonate response to vagal stimulation are not brought about by the same mechanism. An increased release of secretin is not involved. Peptidergic (VIP-containing) nerves may contribute.     

Nervous control of pancreatic exocrine secretion in pigs.

The pancreatic secretion of fluid, bicarbonate and protein in response to electrical stimulation of the vagus and splanchnic nerves, to exogenous and endogenous secretin and to various pharmacological agents was studied in anesthetized young pigs (21 kg). Vagal stimulation increased flow, bicarbonate output and protein output in a frequency dependent manner; the half maximal effective frequency was 2--4 Hz and the maximal effective frequency 12 Hz. The secretory response to vagal stimulation was potentiated by physiological elevations of the arterial concentration of secretin brought about by injection of secretin or by acidification of the duodenal bulb. Simultaneous stimulation of the splanchnic nerves strongly inhibited the response to vagal stimulation; splanchnic nerve stimulation alone had no demonstrable effect. The flow and bicarbonate response to vagal stimulation was unaffected by atropine, but abolished by hexamethonium. Protein output was strongly inhibited by both agents. The response to intraarterial infusion of acetylcholine resembled that elicited by vagal stimulation but it was smaller and it was completely abolished by atropine and unaffected by hexamethonium. Alpha- and beta-adrenergic blockade stimulated rather than inhibited the secretory response to vagal stimulation. The portal vein plasma concentration of secretin was not affected by vagal stimulation. The results indicate that the protein response, and the flow and bicarbonate response to vagal stimulation are not brought about by the same mechanism. An increased release of secretin is not involved. Peptidergic (VIP-containing) nerves may contribute.     

Galanin: effects on basal and stimulated insulin and glucagon secretion in the mouse

Galanin was recently demonstrated to be a neuropeptide in intrapancreatic nerves. In this study, the effects of galanin on basal and stimulated insulin and glucagon secretion in the mouse were investigated. Galanin, injected intravenously at dose levels ranging from 0.53 to 8.5 nmol kg-1, markedly lowered basal plasma insulin levels and transiently increased basal plasma glucagon levels. Furthermore, galanin induced hyperglycaemia: plasma glucose levels were 11 +/- 0.2 mmol l-1 2 min after injection of galanin (4.25 nmol kg-1) compared with 9.3 +/- 0.3 mmol-1 in controls (P less than 0.001). Galanin also impaired the plasma insulin response to either glucose or the cholinergic agonist carbachol. Thus, galanin (4.25 nmol kg-1) inhibited the plasma insulin response to glucose by 65% (P less than 0.001), and that to carbachol by 85% (P less than 0.001). Moreover, glucose abolished the galanin-induced plasma glucagon response. Also, galanin and carbachol exerted additive stimulatory effects on glucagon levels. It is concluded from this study in mice that galanin inhibits basal and stimulated insulin secretion, stimulates glucagon secretion, and induces hyperglycaemia. It is suggested that the intrapancreatic neuropeptide galanin is of importance in the regulation of both insulin and glucagon secretion.     

A gastric phase of pancreatic secretion

1. Extracts of antral mucosa increase the output of pancreatic amylase. They do not stimulate the resting pancreas of the anaesthetized cat to secrete juice, but have a slight `secretin-like' effect on a pancreas already responding to endogenous or exogenous secretin.

2. In animals with the vagus and splanchnic nerves cut instillation of meat extracts or acetylcholine into the antrum stimulates gastric acid and pancreatic amylase secretion. These responses can be prevented by injection of atropine or cocainization of the antral mucosa.

3. In animals with the splanchnic nerves cut but the vagus nerves intact, distension of the body or antrum increases the output of amylase. After vagal section distension of the body has no effect on the pancreas, but the response to antral distension is still present.

4. It is concluded that there is a gastric phase of pancreatic secretion which, in the cat, is almost entirely a stimulation of enzyme output. A vago-vagal reflex pathway is required for the pancreatic response to mechanical stimulation of the body of the stomach, and may be involved in the response to antral stimulation. Chemical and mechanical stimulation of the antrum produces a hormonally mediated increase in pancreatic enzyme secretion. The effects of atropine and cocaine on this response are consistent with the view that the release of the antral stimulant depends on a local cholinergic reflex pathway in the antrum.

     

Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.     

Stimulation of insulin and glucagon secretion by vasoactive intestinal peptide.

In vivo, vasoactive intestinal peptide (VIP) produces simultaneous increases in blood glucose and insulin levels. In order to determine whether VIP, like its homologues, also stimulates insulin secretion directly, studies were made in controlled glucose media employing the vascularly perfused cat pancreas. VIP stimulated insulin secretion significantly in the presence of constant physiological concentrations of glucose. The highest insulin response to VIP (100.3+/-8.1 muU/min) approached the highest insulin response to glucose (119.9 +/- 12.0 muU/min). In the absence of glucose, the insulin response to VIP was insignificant. Unexpectedly, VIP was found to be a more effective stimulant of glucagon than of insulin secretion. The highest glucagon response to VIP (327+/-51% of control levels) was attained in the presence of physiological concentrations of glucose and equalled the glucagon response obtained upon withdrawal of glucose from the perfusate. The glucagon response to VIP was blocked by increasing the glucose in the perfusate. These studies indicate the VIP present in pancreatic islets might play a role in the local control of pancreatic endocrine function.     

Effects of splanchnic nerve stimulation and of clonidine on gastric and duodenal HCO3- secretion in the anaesthetized cat

Experiments were performed on chloralose-anaesthetized cats with ligated adrenals. The vagal and splanchnic nerves were cut and arranged for peripheral electric stimulation. The gastric lumen was perfused with isotonic saline and gastric H+ and HCO3- secretions were calculated from pH/pCO2 measurements in the perfusate. Gastric motility was recorded as changes in hydrostatic pressure in the perfusion circuit. Mucosal HCO3- secretion into the duodenum was monitored in situ by pH-stat titration. Vagal stimulation (10 Hz for 10 min) increased gastric and duodenal HCO3- secretions, as well as gastric motor activity and H+ secretion. Splanchnic nerve stimulation (10 Hz for 10 min) did not affect gastric H+ and HCO3- secretions, but tended to decrease gastric motor tone and basal duodenal HCO3- secretion. Splanchnic nerve stimulation simultaneously with vagal stimulation inhibited gastric contractions and the rise in gastric H+ and duodenal HCO3- secretions observed in response to vagal stimulation alone, but had little effect on the rise in gastric HCO3- secretion. However, such vago-splanchnic stimulation in the presence of the alpha 2-adrenoceptor blocker yohimbine induced gastric contractions, H+ secretory and duodenal HCO3- secretory responses with magnitudes similar to those induced by vagal stimulation alone, whereas the gastric HCO3- secretory response was larger than by vagal stimulation alone. The alpha 2-adrenoceptor agonist clonidine (50 micrograms kg-1 h-1, i.v.) inhibited the gastric contractions and increases in gastric and duodenal HCO3- secretion in response to vagal stimulation, but did not influence vagal stimulation of gastric H+ secretion. The results suggest the existence of a peripheral sympatho-inhibitory action on gastric and duodenal HCO3- secretion involving alpha 2-adrenoceptors. Also splanchnic neural stimulatory effects on gastric and duodenal HCO3- secretion may exist.     

The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf

1. The extent to which the autonomic innervation to the pancreas is implicated in the control of glucagon release during hypoglycaemia has been investigated in calves 3-6 weeks after birth.2. A pronounced rise in plasma glucagon concentration occurred in normal conscious calves in response to hypoglycaemia following administration of insulin (0.1 u./kg). Prior treatment with atropine caused no significant change in the hypoglycaemic response to insulin in these animals but the rise in plasma glucagon concentration was delayed.3. Section of both splanchnic nerves produced no significant change in the tolerance of conscious calves to this small dose of insulin and the changes in plasma glucagon concentration in these animals were within the normal range.4. In contrast, the same dose of insulin produced severe hypoglycaemia, accompanied by convulsions, in atropinized calves with cut splanchnic nerves. In spite of the intensity of the hypoglycaemic stimulus the rise in plasma glucagon concentration was both delayed and diminished in these animals.5. Administration of atropine alone (0.2 mg/kg) to normal fasting calves produced a significant fall in the mean plasma concentrations of both glucose and glucagon (P < 0.01) within 30 min, without affecting that of insulin.6. A significant increase in plasma glucagon concentration also occurred in response to stimulation of the peripheral ends of the thoracic vagi in adrenalectomized calves with cut splanchnic nerves under barbiturate anaesthesia. A rise in mean plasma glucose concentration was also observed in these experiments and found to be significantly correlated with the glucagon response.7. It is concluded that changes in either sympathetic or parasympathetic efferent activity may modify plasma glucagon concentration in the conscious calf, but that only the latter mechanism is likely to be implicated in the response to changes in plasma glucose concentration within the physiological range.     

Myelin basic protein stimulates insulin and glucagon secretion from rat pancreatic islets in vitro and in vivo

The effect of myelin basic protein on insulin and glucagon secretion from rat pancreatic islets was studied in vivo and in vitro. The myelin basic proteins isolated from bovine, human and rat brains all stimulated insulin secretion in a similar fashion. In a static incubation of isolated pancreatic islets, myelin basic protein at doses of 15.6–250 μg in a 0.5-ml reaction volume (1.7 times 10^-8 to 2.7 times 10^-5 M) significantly stimulated hormone release. Maximal stimulation, obtained at the 250-μg dose, was 6.5-fold greater than control for insulin secretion and 6.7-fold greater than control for glucagon secretion. In the case of glucagon no saturation was observed, but saturation was obvious for insulin release at doses of myelin basic protein of 62.5–250μg, larger doses causing permeabilization of the islet membranes as indicated by leakage of acid phosphatase. At a 100-μg dose the time course of insulin secretion induced by myelin basic protein indicated a fast initial release, and after the first 2 h only a little more insulin was released. At the lower doses of myelin basic protein (11 and 33μg) the secretion rate was nearly constant after the first hour. Significant stimulation of glucagon release by myelin basic protein was seen after 60 min, the rate of release being roughly constant at 33-and 100-μg doses thereafter. At the 11-μg dose significant stimulation of hormone release was observed only after a 4-h incubation. Lowering the temperature from 37 to 27 and 20°C reduced both basal and stimulated hormone secretion, the extent of stimulation over the basal level remaining the same at all temperatures only for insulin secretion at a dose of myelin basic protein of 100 μg. A dose of 10 mg myelin basic protein injected intravenously into anaesthetized rats resulted 15 min after injection in a circulating concentration of myelin basic protein of 34.7 μg ml^-1 (1.7 times 10^-6 M) as measured by our radioimmunoassay. It stimulated insulin secretion (P < 0.01), having no significant effect on plasma glucagon levels. Since myelin basic proteins have been shown to display fusogenic properties in cell-free membrane systems, we propose that myelin basic protein exerts its hormone-releasing effect by aggregating and fusing the hormone-containing vesicles to the cell plasma membranes.     

Influence on plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity in peripheral venous blood of anaesthetized cats induced by low intensity afferent stimulation of the sciatic nerve

The objective of the present study was to investigate whether gastrointestinal hormones can be released in response to low intensity afferent activation of the sciatic nerve. Experiments were performed on anaesthetized cats in which the sciatic nerve was stimulated electrically at 3 Hz, to V and 0.2 ms. Blood samples were collected in a peripheral vein and the plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity (below referred to as somatostatin, gastrin, glucagon, insulin and VIP) were recorded by radioimmunoassay. Afferent stimulation of the sciatic nerve caused immediate (approximately 15 min long) changes of the levels of all the above mentioned peptides. Somatostatin, gastrin and glucagon levels rose significantly, whereas in the case of insulin and VIP a significant relationship between the effect of sciatic nerve stimulation and basal levels was established. Thus, insulin and VIP levels decreased when basal levels were high and increased when basal levels were low. The secretion of gastrointestinal and pancreatic hormones is in part regulated by the autonomic nervous system. It is suggested that afferent stimulation of the sciatic nerve causes a reflex activation of the vagal and/or the splanchnic nerves, which in turn affects the release rate of the above-mentioned hormones. In conclusion, these data show that the release of gastrointestinal hormones can be influenced by low intensity stimulation of the sciatic nerve. The physiological trigger of these responses may be touching of the skin.     

Adrenergic influence on bile secretion—an experimental study in the cat

The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h^-1 kg^-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an α-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly α-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a β-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the α-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.     

Effects of splanchnic nerve stimulation and of clonidine on gastric and duodenal HCO-3 secretion in the anaesthetized cat

Experiments were performed on chloralose-anaesthetized cats with ligated adrenals. The vagal and splanchnic nerves were cut and arranged for peripheral electric stimulation. The gastric lumen was perfused with isotonic saline and gastric H⁺ and HCO₃^-secretions were calculated from pH/pCO₂ measurements in the perfusate. Gastric motility was recorded as changes in hydrostatic pressure in the perfusion circuit. Mucosal HCO₃^- secretion into the duodenum was monitored in situ by pH-stat titration. Vagal stimulation (10 Hz for 10 min) increased gastric and duodenal HCO₃^- secretions, as well as gastric motor activity and H⁺ secretion. Splanchnic nerve stimulation (10 Hz for 10 min) did not affect gastric H⁺ and HCO₃^- secretions, but tended to decrease gastric motor tone and basal duodenal HCO₃^- secretion. Splanchnic nerve stimulation simultaneously with vagal stimulation inhibited gastric contractions and the rise in gastric H⁺ and duodenal HCO₃^- secretions observed in response to vagal stimulation alone, but had little effect on the rise in gastric HCO₃^- secretion. However, such vago-splanchnic stimulation in the presence of the α₂^- adrenoceptor blocker yohimbine induced gastric contractions, H⁺ secretory and duodenal HCO₃^- secretory responses with magnitudes similar to those induced by vagal stimulation alone, whereas the gastric HCO₃^- secretory response was larger than by vagal stimulation alone. The α₂^-adrenoceptor agonist clonidine (50 μg kg^-1 h- ¹ , i.v.) inhibited the gastric contractions and increases in gastric and duodenal HCO₃^- secretion in response to vagal stimulation, but did not influence vagal stimulation of gastric H⁺ secretion. The results suggest the existence of a peripheral sympatho-inhibitory action on gasmc and duodenal HCO₃^-secretion involving α₂^-adrenoceptors. Also splanchnic neural stimulatory effects on gastric and duodenal HCO₃^- secretion may exist.     

Evidence for central timing of rhythmical mastication

1. Electrical stimulation of the vagus nerves produced a parallel increase in gastric acid secretion and gastric mucosal blood flow.

2. Gastric acid secretion and mucosal blood flow, stimulated by pentapeptide infusions or by vagal stimulation, were markedly and equally reduced by electrical stimulation of splanchnic nerve fibres.

3. The splanchnic stimulated reduction in acid and mucosal blood flow occurred only when the rise in blood pressure, normally associated with splanchnic stimulation, was prevented by inclusion of a pressure reservoir in the circulation.

4. There was evidence that the effect of the splanchnic nerves was not mediated by release of adrenaline from the adrenal medulla.

     

Sympatho-adrenergic inhibition of vagally induced gastric motility and gastroduodenal HCO-3 secretion in the cat

Chloralosed cats were acutely vagotomized and their adrenal glands were ligated. The gastric lumen was perfused with isotonic NaCl and gastric motility was recorded as change in hydrostatic pressure within the perfusion circuit. Gastric secretions of H+ and HCO3- were calculated from continuous measurements of pH and pCO2 in the perfusate. Mucosal HCO3- secretion in the distal duodenum was titrated in situ by pH-stat equipment. The experiments were divided into three different groups dependent on the state of sympathetic splanchnic nervous supply: intact; cut on a preganglionic level; blocked with the adrenolytic agent guanethidine. Basal levels for gastric motility, gastric H+ and HCO3- secretions and duodenal HCO3- secretion were more or less similar in all groups. Gastric motility, gastric HCO3- and duodenal HCO3- secretory responses to bilateral vagal stimulation were significantly enhanced in splanchnicotomized or guanethidine-treated animals as compared to controls with intact sympathetic supply. However, no clear differences in gastric H+ secretory responses to vagal stimulation were demonstrated between animals with an intact or disrupted sympathetic innervation. These results suggest a sympatho-adrenergic inhibitory action on vagally induced mucosa-protective HCO3- secretion in the stomach and the duodenum. Furthermore, vagal stimulation in animals with intact splanchnic nerves induced a guanethidine-resistant delayed increase in duodenal HCO3- secretion. The nature of this response was not further analysed.