[The enteric nervous system. Untested field for specific pharmacotherapy].
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Digestive System↗
Biomedical subjects
L Fändriks
Publications and source records attributed to L Fändriks.
Sympatho-adrenergic inhibition of basal and acid-induced changes in duodenal motility, mucosal net fluid and alkaline secretion in the anaesthetized cat.
Experiments were performed on chloralose anaesthetized cats. A 2-cm segment of the proximal duodenum was isolated between two luminally situated balloons and perfused with isotonic saline containing [14C]-PEG 4000 as a non-absorbable marker. The perfusate was analysed with regard to alkalinity (back titration) and concentration of marker (liquid scintillation). Net alkalinization and net fluid transport were calculated with conventional equations. Motor activity in the duodenal wall was recorded as changes in volume of the proximal balloon. In presence of sympathetic neural activity (spontaneous or electrically stimulated) basal motor activity and mucosal alkaline secretion was low and increased minimally in response to luminal HCl (30 mM). Net fluid transport was in an absorptive state and shifted to a small secretion upon the acid-exposure. Subsequent to bilateral acute splanchnicotomy, or the administration of the adrenolytic guanethidine (3-4 mg kg-1, i.v.), spontaneous duodenal contractions occurred and the alkaline secretion was increased. Furthermore, both parameters were then markedly stimulated by luminal perfusion with 30 mM HCl. Basal net fluid transport was zero and turned into secretion upon the acid-exposure. No morphological changes of the duodenal surface epithelium could be detected. The study demonstrates the existence of splanchnic nerve-mediated, adrenergic inhibition of basal, as well as of acid-induced duodenal motility, fluid and alkaline secretion.
Animals↗
Gastric output of IgA in man: relation to migrating motility complexes and sham feeding.
BACKGROUND/AIMS: The immunologic reactivity of the gastric mucosa is poorly understood. The origin and dynamics of immunoglobulin A (IgA) occurring in the gastric lumen were investigated in healthy, Helicobacter pylori-negative volunteers. METHODS: Gastroduodenal manometric motility recordings were combined with gastric luminal perfusion, enabling calculation of gastric acid output and analysis of the total IgA output. RESULTS: Acid output and total IgA correlated with the migrating motility complexes (MMC). The gastric IgA release showed maximal values in association with gastric motility phase III (maximal motor activity) and lowest values during phases I and II (none or irregular motor activity). The IgA output correlated with neither swallowed saliva (as indicated by amylase in the gastric perfusate) nor duodenogastric reflux (as indicated by gastric occurrence of bilirubin and/or duodenally infused PEG4000). Stimulation of gastric acid secretion by sham feeding during phase II-like motor activity (n = 6) induced a rapid and transient doubling of IgA output. There was no significant correlation between gastric acid secretion and gastric IgA release. CONCLUSION: Substantial amounts of IgA are released into the human stomach, most likely originating from the gastric mucosa. The up-regulation of IgA release in association with the activity front of the MMC and anticipatory to food intake suggests a neuroendocrine control of gastric mucosal immune responses.
Adult↗
Accumulation of an endogenous inhibitor of nitric oxide synthase during graded hemorrhagic shock.
Asymmetric dimethylarginine (ADMA) represents an endogenous inhibitor of nitric oxide (NO) production. The production of ADMA has been shown to increase during cellular stress, e.g., hypoxia. Furthermore, ADMA has recently been reported to accumulate in plasma during terminal renal failure as a consequence of diminished urinary excretion. Since tissue hypoxia and oliguria are both characteristics of severe hemorrhagic shock, this study was performed in order to establish whether plasma concentrations of ADMA increase during hemorrhagic shock. Six pigs were subjected to graded hemorrhage (20% and 40% of the calculated blood volume), resulting in significant (P < 0.05) reductions in blood pressure and cardiac output (from 98 +/- 4 to 36 +/- 5 mm Hg and from 3.0 +/- 0.2 to 1.4 +/- 0.2 L/min, respectively). Plasma ADMA concentrations as determined by high-performance liquid chromatography (HPLC) increased from a pre-hemorrhage value of 3.4 +/- 0.3 microM to 3.9 +/- 0.4 microM (ns) and 5.2 +/- 0.4 microM (P < 0.05), respectively. The present study demonstrates that plasma ADMA concentrations increase significantly during hemorrhagic shock. Thus, inhibition of the arginine-nitric oxide pathway as a result of ADMA accumulation, may represent an additional physiological mechanism to maintain systemic blood pressure in response to acute hypovolemia.
Amino Acid Oxidoreductases↗
The mediation of increased duodenal alkaline secretion in response to 10 mM HCl in the anaesthetized rat. Support for the involvement of capsaicin-sensitive nerve elements.
Experiments were performed on chloralose-anaesthetized rats. Bicarbonate secretion by the duodenal mucosa was continuously recorded by use of an in situ-titration technique. Exposing the duodenal segment to 10 mM HCl over 5 min increased the bicarbonate transport by about 65%. This acid-induced secretory response was resistant to neural decentralization by means of bilateral cervical vagotomy and/or splanchnicotomy. Furthermore, in the decentralized state, serosal application of the local anaesthetic lidocaine or tetrodotoxin (TTX) lowered basal duodenal bicarbonate secretion. Despite the presence of lidocaine or TTX, exposure of the duodenal mucosa to 10 mM HCl induced a net increase in secretion with a magnitude similar to that observed in the control situation with intact nerves. A 5-min exposure period of the decentralized duodenal segment to capsaicin (1.2 mg ml-1) raised bicarbonate secretion, a response which also occurred in the presence of lidocaine (serosa). Tachyphylaxis to capsaicin blocked the secretory response to 10 mM HCl and inhibited the response to luminal prostaglandin E2 (1.5 10(-5) M) by 80%. The present results indicate that luminal exposure to 10 mM HCl activates capsaicin-sensitive primary afferents which, locally within the submucosa or epithelium, activate the bicarbonate secretion.
Animals↗
Hypovolaemia inhibits acid-induced alkaline transport in the rat duodenum via an alpha-2 adrenergic mechanism.
Acid exposure of the duodenal mucosa is a well-known stimulant of the mucosal alkaline secretion. We have previously reported that a minor blood loss inhibits this secretory increment via activation of the splanchnic nerves. In the present study the pharmacological characteristics of the splanchnic neural inhibition of the alkaline secretion were investigated. Duodenal HCO3- secretion was measured by in-situ titration in chloralose-anaesthetized rats. Exposure of the duodenal mucosa to hydrochloric acid (0.01 M, 5 min) increased the secretion by approximately 60%. A 10% decrease in blood volume simultaneously to the luminal acidification abolished the secretory increase, as previously reported. Treatment with either guanethidine or yohimbine blocked the bleeding-induced inhibition of the secretion after acid-exposure. Neither prazosin nor propranolol did prevent such hypovolaemia-induced inhibition of duodenal alkaline secretion. The present results suggest that the splanchnic neural inhibition of acid-induced duodenal HCO3- secretion is mediated via adrenergic nerve fibres and alpha-2 adrenoceptors.
Animals↗
Gastric bicarbonate secretion, acid secretion, and mucosal blood flow during influence of pentagastrin and omeprazole in the cat.
In this study secretion of bicarbonate and acid and mucosal blood flow were determined simultaneously in cats. The gastric lumen of anesthetized cats was continuously perfused with isotonic saline. Secretion of HCO-3 and H+ was calculated from continuous measurements of pH and PCO2 in the perfusate. Mucosal blood was measured by means of radiolabeled microspheres. Under resting acid secretory conditions, bicarbonate secretion into the gastric lumen averaged 1.0 mumol/min. Somewhat surprising, both omeprazole (4 mg/kg as bolus) and pentagastrin (16 micrograms/kg.h intravenously) significantly reduced the HCO-3 secretion. Omeprazole did not influence mucosal blood flow, whereas corpus mucosal blood flow increased during pentagastrin stimulation. Under resting acid secretory conditions and during omeprazole treatment there was a close linear relationship between acid and bicarbonate secretion. No such relationship was found during pentagastrin stimulation of the mucosa. No consistent relationship was obtained between blood flow and bicarbonate secretion in normal gastric mucosa.
Animals↗
Effects of cigarette smoke and nicotine on duodenal bicarbonate secretion in the rabbit and the rat.
The effects of short-time exposure to cigarette smoke on duodenal mucosal bicarbonate secretion were studied in anesthetized rabbits and rats. The bicarbonate secretion was measured by continuous titration of recirculating luminal perfusate. In artificially ventilated rabbits, intermittent exposure to cigarette smoke during two 10-min periods caused a marked (approximately 40%) decrease (p less than 0.01) in duodenal bicarbonate secretion. After the exposures, secretion gradually recovered and had returned to the pre-exposure rate after 50 min. The decrease in secretion was associated with decreases in heart rate (approximately 15%) and blood pressure (approximately 30%) that, however, were of shorter duration. Neither reduced amounts of smoke (1/6 or 1/3) nor nicotine (25-1,000 micrograms/kg, intravenously) had any major effect on the bicarbonate secretion. In the spontaneously breathing rat, smoke was administered for 1-2 breaths every 30 s during a 5-min period. This exposure resulted in a significant (p less than 0.05) decrease in bicarbonate secretion and some increase in the blood pressure. Exposure to smoke had no effect on the secretion in rats with both splanchnic nerves cut, suggesting neural sympathetic mediation of the smoke-induced inhibition.
Animals↗
Vagal and sympathetic control of gastric and duodenal bicarbonate secretion.
This report summarizes data concerning the extrinsic neural control of bicarbonate secretion by the gastric and duodenal mucosa. Parasympathetic vagal effects have been studied in experimental animals and in man by means of direct electrical vagal stimulation, sham-feeding procedures and intracerebroventricular peptide injections. The results show that the vagal nerves have a stimulatory effect on gastroduodenal bicarbonate secretion. Furthermore, both conventional nicotinic and muscarinic cholinoceptor, as well as non-cholinergic transmission, mediate the vagal effect. Sympathetic splanchnic nerve effects have been investigated by means of nerve sections, direct electrical stimulation, reflex activation and stereotaxic electrical hypothalamic stimulation. The data show that the splanchnic nerves have a predominantly inhibitory action on gastroduodenal bicarbonate secretion by use of peripheral adrenergic neurones and receptors of the alpha-2 subtype. The role of the adrenal glands is not fully understood. It is concluded that gastroduodenal bicarbonate secretion is under autonomic neural control, mainly in the classical antagonistic fashion; the parasympathetic vagal nerves stimulate bicarbonate output, whereas the sympathetic splanchnic nerves are mainly inhibitory.
Acid-Base Equilibrium↗
Studies of cholera toxin-induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo.
A pH-stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10-25% by hexamethonium (10 mg kg-1 body wt i.v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg-1 body wt i.v.) had no effect. Thus the cholera toxin-induced alkaline secretion in the jejunum is attributed mainly to a non-nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT-evoked increased transport of the coupled Na+/H+ and Cl-/HCO3- exchangers, which cannot be measured with the pH-stat technique used in this study.
Animals↗
Effects of acute administration of omeprazole or ranitidine on basal and vagally stimulated gastric acid secretion and alkalinization of the duodenum in anaesthetized cats.
Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. In order to avoid sympathoadrenergic influences, the adrenal glands were ligated and the splanchnic nerves were cut bilaterally in all animals. The gastric lumen was perfused with saline and the H+ secretion was calculated from pH measurements in the perfusate. HCO3- secretion by the duodenal mucosa was titrated in situ. Omeprazole (4 mg kg-1 i.v., dissolved in PEG400, 40% w/v) did not influence basal or vagally induced HCO3- secretions, but inhibited by about 80% the H+ secretory response induced by electric vagal stimulation. Acute administration of ranitidine (5 mg kg-1 i.v.) transiently lowered arterial pressure, an effect which was followed by a sustained compensatory tachycardia. Ranitidine raised basal duodenal HCO3- secretion by 50% and inhibited vagally induced gastric H+ secretion by about 70%, whereas vagally induced HCO3- secretion was not influenced. The results suggest that vagal nerve stimulation raises the duodenal bicarbonate secretion via a mechanism independent of the level of gastric H+ secretion.
Anesthesia↗
Effects of hypovolemia on blood flow, arterial [HCO3-], and HCO3- output in the rat duodenum.
The effects of bleeding-induced hypovolemia on duodenal blood flow (microsphere technique), arterial [HCO3-], and duodenal HCO3- secretion (in situ titration) were investigated in chloralose-anesthetized rats. A 10% decrease in blood volume reduced duodenal HCO3- secretion by 44%, duodenal blood flow by 31%, and arterial [HCO3-] by 11%. In a group with cervically cut vagal nerves, basal duodenal HCO3- secretion was greater than 50% lower compared with controls. Basal blood flow and arterial [HCO3-] were on similar levels as in nonvagotomized animals. Furthermore, bleeding failed to lower duodenal alkaline output in rats with cut vagal nerves, although blood flow and arterial [HCO3-] were reduced to a similar extent as in the vagally intact controls. In a yohimbine-treated group, a 10% bleeding reduced duodenal blood flow by 28% and arterial [HCO3-] by 7% without influencing duodenal HCO3- secretion. We suggest that the hypovolemia-induced inhibition of duodenal alkaline secretion is not caused by a decrease in blood and/or arterial [HCO3-]. Instead, other factors may be of importance, for example, neural effects on enteric secretomotor neurons or directly on the secreting epithelium.
Animals↗
Splanchnic nerve activation inhibits the increase in duodenal HCO3- secretion induced by luminal acidification in the rat.
Acid exposure of the duodenal mucosa increased duodenal HCO3- secretion by approximately 60%. When the acid exposure was performed simultaneously with an arterial bleeding of 0.6 ml/100 g body wt (10% of the total blood volume), the increase in duodenal HCO3- secretion was totally abolished. When the acid exposure and bleeding procedures were performed at the same time in rats with bilaterally cut splanchnic nerves, alkaline secretion increased by 60%, as it did in the unbled rats. Direct electrical stimulation of the splanchnic nerves (10 Hz, supramaximal intensity) inhibited the stimulatory effect of duodenal acid exposure on alkaline secretion. Taken together, the data suggest that the sympathetic nervous system, because of splanchnic nerve activation, inhibits the acid-induced increase in duodenal HCO3- secretion.
Animals↗
Influences of the sympatho-adrenal system on gastric motility and acid secretion and on gastroduodenal bicarbonate secretion in the cat.
Experiments were performed on acutely vagotomized cats during chloralose anaesthesia. Gastric H+ and HCO3- secretions were calculated from the pH and PCO2 in a luminal perfusate. Gastric motility was reflected by changes in hydrostatic pressure within the luminal perfusion system ('intragastric pressure'). Duodenal HCO3- secretion was monitored by pH titration in situ. Animals with an intact sympatho-adrenal system (group 1) were compared with others subjected to splanchnicotomy (group 2), adrenal gland ligation (group 3), and splanchnicotomy plus adrenal gland ligation (group 4). Basal gastric H+ secretion, as well as vagally induced H+ secretory responses, did not differ significantly between groups. Basal gastric HCO3- secretion was lower in all groups with a manipulated sympatho-adrenal system compared to the intact controls. Vagally induced increases in gastric HCO3- secretion were enhanced in the splanchnicotomized groups (groups 2 and 4). Basal as well as vagally induced increases in intragastric pressure and duodenal HCO3- secretion were enhanced in animals subjected to splanchnicotomy, with or without simultaneous adrenal gland ligation (groups 2 and 4). Adrenal gland ligation per se had no such effects. The results suggest that the adrenal glands exert a stimulatory action on basal gastric HCO3- secretion. Basal intragastric pressure and basal duodenal HCO3- secretion are inhibited by post-ganglionic sympathetic neurons, not involving the adrenal glands. Also, vagal excitatory effects on gastric motility, as well as on gastric and duodenal HCO3- secretions, are inhibited by such a direct neural mechanism.
Adrenal Glands↗
Increased duodenal HCO3- output after blood volume expansion in the rat: an effect mediated by atrial natriuretic peptide (ANP)?
Duodenal HCO3- secretion was measured by in-situ titration in chloralose-anaesthetized rats. The effects of hypervolaemia, induced by i.v. injections of an albumin infusion, on duodenal HCO3- secretion were investigated. A 10% increase in blood volume increased duodenal HCO3- secretion by about 50%, and this effect was unaffected by splanchnicotomy. If the splanchnicotomy was combined with cervical vagotomy, the basal HCO3- secretion was lower but the increase in secretion after 10% blood volume expansion with albumin was still 50%. If the same increase in blood volume was produced in splanchnicotomized and vagotomized rats in which the right atrial appendix had been removed, a procedure that markedly reduces the ANP (atrial natriuretic peptide)-producing cells, no increase in secretion could be observed. Intravenous injections of alpha-r-ANP (10 micrograms kg-1 and 30 micrograms kg-1) increased duodenal HCO3- secretion in a dose-dependent fashion. Based on the present findings, we suggest that hypervolaemia increases duodenal HCO3- secretion via release of ANP from the heart.
Animals↗
Hypothalamic inhibition of duodenal alkaline secretion via a sympatho-adrenergic mechanism in the rat.
Experiments were performed on rats anaesthetized with chloralose. A duodenal segment was perfused with recirculating isotonic saline, and alkalinization of this perfusate (HCO3- secretion) was measured by continuous pH-stat titration. Stereotaxic electric unipolar stimulations were performed in the perifornical region of the hypothalamus. Stimulation points eliciting an increased arterial pressure were stimulated for a period of 15 min. Duodenal HCO3- secretion decreased in 19 out of 25 experiments and increased in four out of 25 experiments. Inhibitory responses to hypothalamic stimulation were blocked either by thoracic epidural anaesthesia or by the adrenolytic agent guanethidine, suggesting a spinal pathway to the duodenum, presumably in the thoracic splanchnic nerves, and involvement of adrenergic neurons.
Anesthesia, Epidural↗
Afferent electrical stimulation of mesenteric nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of the splanchnic nerves in the rat.
The experiments were performed on male Sprague-Dawley rats anaesthetized with chloralose. Duodenal HCO3- secretion was measured in situ by pH-stat titration. The nerves bundles surrounding two randomly chosen mesenteric vessels were electrically stimulated (3 Hz, supramaximal intensity) in the afferent direction. This was done in order to mimic the intestino-intestinal spinal reflex activation of the splanchnic sympathetic fibres. The procedure reduced duodenal HCO3- secretion by 20% together with an increase in mean arterial pressure and heart rate. Duodenal HCO3- secretion decreased similarly in control rats and in those subjected to a cervical cord transection, whereas animals with bilaterally cut splanchnic nerves did not respond to such mesenteric nerve stimulation. Pharmacological pretreatment with guanethidine or yohimbine, but not prazosin, inhibited the reduction in duodenal HCO3- secretion. Thus the data suggest that electrical stimulation of mesenteric afferent nerves inhibits duodenal HCO3- secretion via a spinal reflex activation of splanchnic sympathetic nerve fibres to the duodenum, and that the response is mediated via alpha 2 adrenoceptors.
Afferent Pathways↗
Splanchnic nerve stimulation inhibits duodenal HCO3- secretion in the rat.
Sympathoadrenergic inhibition of HCO3- secretion by the duodenal mucosa was studied in chloralose anesthetized rats. Duodenal HCO3- secretion was measured in situ by pH-stat titration. Direct efferent electrical stimulation of the cut splanchnic nerves (10 Hz, supramaximal intensity) inhibited the duodenal alkaline output by approximately 50%. This inhibitory response was blocked by the administration of either the adrenolytic agent guanethidine or the alpha 2-adrenoceptor antagonist yohimbine. However, neither the alpha 1-adrenoceptor antagonist prazosin nor the beta-adrenoceptor antagonist propranolol blocked the response to splanchnic nerve stimulation. The present data suggest that electrical splanchnic nerve stimulation inhibits duodenal HCO3- secretion via activation of adrenergic nerve fibers and alpha 2-adrenoceptors within the peripheral nervous system.
Animals↗