Effect Of Splanchnic Nerve Stimulation Research Articles

Raising the pressure: Hemodynamic effects of splanchnic nerve stimulation.

A number of cardiovascular and neurological diseases are characterized by a dysregulation of intravascular volume distribution. The veins and arteries of the visceral organs form the so-called splanchnic vascular compartment and are the largest reservoir for intravascular blood. The blood localized in the splanchnic compartment can be mobilized in and out of the compartment via passive compression or active neurohormonal recruitment. We studied the hemodynamic effects of splanchnic nerve stimulation during five cases of irreversible electroporation (IRE) in patients with pancreatic cancer. In IRE, repeated bursts of high-voltage electrical fields are applied to visceral beds for >1 min, which induces rapid increase in blood pressure, heart rate, and cardiac output. We present the first analysis into the hemodynamic changes with splanchnic nerve stimulation and explore potential mechanisms of the hyperdynamic state. Our analysis presents the first human report of splanchnic nerve stimulation to induce hypertension and volume redistribution, introducing the splanchnic nerves as a key component of cardiovascular regulation.NEW & NOTEWORTHY Our case series provides the first detailed description of human hemodynamic effects with splanchnic nerve stimulation. Splanchnic nerve stimulation results in profound hemodynamic alteration with rapid onset of hypertension and blood mobilization.

Hydrogen Sulfide Selectively Potentiates Central Preganglionic Fast Nicotinic Synaptic Input in Mouse Superior Mesenteric Ganglion

Hydrogen sulfide (H2S) plays important roles in the enteric system in the wall of the gastrointestinal tract. There have been no studies on whether H2S is endogenously generated in peripheral sympathetic ganglia and, if so, its effect on synaptic transmission. In this study, we examined the effect of H2S on cholinergic excitatory fast synaptic transmission in the mouse superior mesenteric ganglion (SMG). Our study revealed that NaHS and endogenously generated H2S selectively potentiated cholinergic fast EPSPs (F-EPSPs) evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. The H2S-producing enzyme cystathionine-γ-lyase (CSE) was expressed in both neurons and glial cells. The CSE blocker PAG (dl-propargylglycine) significantly reduced the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Inhibiting the breakdown of endogenously generated H2S with stigmatellin potentiated the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Splanchnic F-EPSPs but not colonic F-EPSPs were reduced in CSE knock-out (KO) mice. Functional studies showed that NaHS enhanced the inhibitory effect of splanchnic nerve stimulation on colonic motility. Colonic motility in CSE-KO mice was significantly higher than colonic motility in wild-type mice. We conclude that endogenously generated H2S acted selectively on presynaptic terminals of splanchnic nerves to modulate fast cholinergic synaptic input and that this effect of H2S modulates CNS control of gastrointestinal motility. Our results show for the first time that the facilitatory effect of endogenous H2S in the mouse SMG is pathway specific.

A Pilot Study to Evaluate the Effect of Splanchnic Nerve Stimulation on Body Composition and Food Intake in Rats

Systemic sympathetic stimulation with caffeine and ephedrine increased metabolic rate, reduced food intake, and improved body composition but had systemic adverse events. We hypothesize that selective sympathetic stimulation of the upper gastrointestinal tract will preserve the advantages of systemic sympathetic stimulation without its adverse events. This study evaluated the effect of splanchnic nerve stimulation on metabolic rate, food intake, and body composition. Sixteen Sprague Dawley rats had monopolar electrodes placed on the superior common splanchnic nerve innervating the celiac ganglia. An indifferent electrode was placed subcutaneously on the back. The animals were placed on a 60% fat diet, and eight rats were stimulated for 6 weeks. The stimulation was advanced over 3 days from 0.6 mA to 3 mA. Metabolic rate and food intake were measured daily; weight change was monitored weekly, and body composition was determined by nuclear magnetic resonance (NMR) at the end of the study. Four of the eight animals had metabolic rate measured three times over 2-day periods at 0 mA, 1 mA, and 3 mA of stimulation in a metabolic chamber. Except for the first week of stimulation, there was no difference in body weight between the stimulated and control groups. Cumulative food intake was less in the stimulated group (p<0. 001). The lean-to-fat ratio was greater in the stimulated group (p<0. 01), and the animals that received incremental stimulation showed significantly augmented metabolic rate (p<0. 02). Splanchnic nerve stimulation decreased food intake, increased metabolic rate, and improved body composition.

Effect of Splanchnic Nerve Stimulation on Epinephrine and Norepinephrine Release from Gastrointestinal Sympathetic Postganglionic Endings in the Frog.

Gastrointestinal vascular perfusates in bullfrogs before and after splanchnic nerve stimulation were collected and analyzed for epinephrine and norepinephrine. Catecholamine in the perfusate before stimulation was predominantly epinephrine. Upon stimulation a marked increase in epinephrine release without any significant change in norepinephrine release was observed in experiments at 8-10 degrees C as well as 16-21 degrees C, showing that in frogs epinephrine is the sympathetic neurotransmitter and that the release of epinephrine is not affected by low temperatures.

Antisecretory effect of splanchnic nerve stimulation on choleratoxin‐induced secretion in the cat, an effect mediated at the crypts

The experiments were performed on cats anaesthetized with alpha-chloralose. Segments of the small intestine were perfused with sodium-free hypotonic choline-mannitol solution and intestinal net fluid transport was recorded with a volumetric technique. The content of sodium and chloride in the lamina propria of the small intestinal villus was measured with an electron microprobe in freeze-dried paraffin embedded tissue. In absorbing control intestine, there was an even distribution of electrolytes along the villi. Sympathetic nerve stimulation (5 Hz, 5 ms, 5 V) did not significantly affect electrolyte distribution and net fluid transport. Intestinal secretion was elicited by pretreatment of the intestine with cholera toxin. The concentration of sodium and chloride was elevated in the apical third of the villi in intestines during the secretion since secreted sodium from the crypts was reabsorbed into the villi. Sympathetic nerve stimulation decreased the cholera secretion significantly in intestines pretreated with cholera-toxin. Furthermore, the apical gradients of sodium and chloride in the villi, caused by the reabsorbed sodium and chloride, disappeared during sympathetic nerve stimulation. It is concluded that, in the used experimental model, the antisecretory effect of sympathetic nerve stimulation was caused by inhibition of crypt secretion and not by augmented villus absorption.

The effect of splanchnic nerve stimulation on the uptake of atrial natriuretic peptide by the adrenal gland in conscious calves

A technique has been developed with which it has been possible to quantify the output of a wide variety of agonists including catecholamines, glucocorticoids, mineralocorticoids, enkephalins and various peptides, from the adrenal gland in the conscious unrestrained calf; also to investigate responses to electrical stimulation of the peripheral end of the splanchnic nerve below any behavioural threshold. In the present study this methodology has been employed to investigate the extent to which stimulation of the splanchnic sympathetic innervation affects adrenal handling of atrial natriuretic peptide as this peptide has been identified within the adrenal medulla in this species. Stimulation of the splanchnic nerve at frequencies which raised the concentration of atrial natriuretic peptide like-immunoreactivity (ANP) by 25% led to an abrupt increase in the uptake of the peptide by the right adrenal gland by about 250%. During nerve stimulation more than 20% of the ANP that was estimated to be presented to the gland was taken up, by comparison with less than 13% of the amount presented which was taken up before and after stimulation. These results suggest that stimulation of the splanchnic nerve may specifically enhance the uptake of ANP by the adrenal gland and represent the first report of such a mechanism in respect of any biologically active peptide so far as we are aware.

Effects of Splanchnic Nerve Stimulation on the Adrenal Cortex May Be Mediated by Chromaffin Cells in a Paracrine Manner

The effects of nerve activation and of the catecholamines epinephrine and norepinephrine on adrenal corticosteroid release were investigated in intact isolated perfused pig adrenals with preserved nerve supply. To study the contact zones of medullary and cortical tissues, porcine adrenals were examined on the histological and ultrastructural levels. Splanchnic nerve activation stimulated in parallel the release of epinephrine (from a basal value of 0.31 +/- 0.11 to 8.13 +/- 0.60 microgram/min) and norepinephrine (from 0.76 +/- 0.68 to 12.94 +/- 3.58 micrograms/min) and the release of the corticosteroids cortisol (from 0.62 +/- 0.19 to 2.00 +/- 0.35 micrograms/min) and aldosterone (from 3.34 +/- 0.59 to 7.53 +/- 1.63 ng sigma in). Also, perfusion of the isolated adrenals with catecholamines provoked a significant release of the corticosteroids. Epinephrine (10(-6) M) stimulated the release of cortisol (from 0.59 +/- 0.31 to 2.66 +/- 0.34 micrograms/min) and aldosterone (from 2.12 +/- 0.42 to 4.68 +/- 0.92 ng/min). Norepinephrine (10(-6) M) stimulated the release of cortisol (from 0.26 +/- 0.07 to 1.28 +/- 0.10 micrograms/min) and aldosterone (from 1.28 +/- 0.37 to 3.57 +/- 0.80 ng/min). Using an immunostaining for synaptophysin, which is specific for neuroendocrine cells, chromaffin cells could be detected within all three zones of the adrenal cortex. The two endocrine tissues appear to be closely interwoven. On the ultrastructural level, medullary cells are in apposition to cortical cells, with close cellular contacts. These results show that the release of corticosteroids cortisol and aldosterone can be stimulated through the sympatho-adrenal system. Taking into consideration the close colocalization of cortical and medullary tissues, this stimulation may be mediated by chromaffin cells in a paracrine manner.

The effect of splanchnic nerve stimulation and neuropeptide Y on cholera secretion and release of vasoactive intestinal polypeptide in the feline small intestine.

The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.

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.

Effects of adrenoceptor antagonists on vagally induced gastric and duodenal HCO3- secretions in the cat.

Experiments were performed on chloralosed cats with ligated adrenal glands. The cervical vagi were cut and arranged for electric stimulation. The gastric lumen was continuously perfused, and the secretions of H+ and HCO3- were calculated from pH/pCO2 measurements in the perfusate. Gastric motility was recorded as changes in hydrostatic pressure within the perfusion system. Mucosal HCO3- secretion into a duodenal segment, distal to the papilla of Vater and Brunners gland area, was titrated in situ by a pH-stat equipment. Animals pretreated with various adrenoceptor blockers or splanchnicotomy were compared with control animals with intact sympatho-adrenergic system. Basal gastric motor activity, H+ and HCO3- secretions, as well as duodenal HCO3- secretion were not influenced by prazosin, propranolol or splanchnicotomy. Yohimbine increased significantly basal gastric HCO3- secretion, but did not influence basal gastric motor activity, H+ secretion or duodenal HCO3- secretion. Vagal stimulation in yohimbine-treated or splanchnicotomized animals induced significantly larger gastric contractions, HCO3- secretory and duodenal HCO3- secretory responses than in the controls, whereas these responses to vagal stimulation were small in prazosin- or propranolol-treated animals. Vagally induced gastric H+ secretory responses were significantly larger in propranolol-treated animals than in controls, whereas prazosin-treated, yohimbine-treated or splanchnicotomized animals in this regard did not differ from the controls. The results suggest the existence of a sympathetic, probably alpha-2-adrenergic, inhibition of vagally induced gastric contractions as well as of the gastric and duodenal HCO3- secretions.

The effect of splanchnic nerve stimulation on adrenocortical activity in conscious calves.

1. Right adrenal and various cardiovascular responses to stimulation of the peripheral end of the right splanchnic nerve have been investigated in the presence and absence of exogenous adrenocorticotrophin, ACTH1-24, (5 ng min-1 kg-1). The adrenal-clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-4 days previously. 2. The I.V. infusion of ACTH1-24 increased mean plasma ACTH concentration by about 1200 pg/ml and mean right adrenal cortisol output by about 500 ng min-1 kg-1. Stimulation of the peripheral end of the right splanchnic nerve at 4 Hz for 10 min produced a further rise in cortisol output, amounting to about 400 ng min-1 kg-1 (P less than 0.01). These changes in output were reflected accurately by changes in peripheral plasma cortisol concentration. 3. Closely similar amounts of adrenaline were released in response to splanchnic nerve stimulation in the presence and absence of exogenous ACTH. In the presence of ACTH the average mean output of noradrenaline (58 +/- 2 ng min-1 kg-1) was significantly less than that of adrenaline (102 +/- 4 ng min-1 kg-1; P less than 0.001), whereas the corresponding values were not significantly different in the absence of ACTH. 4. These results also confirm the fact that the fall in adrenal vascular resistance which occurs during splanchnic nerve stimulation is substantially reduced by ACTH, as is the rise in met5-enkephalin output. 5. It is concluded that the splanchnic innervation is capable of enhancing the secretion of adrenal glucocorticoids in response to ACTH under physiological conditions in the conscious calf.

Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas

The effect of electrical stimulation of the splanchnic and the vagus nerve supply to isolated, perfused pig pancreas on the secretion of insulin, glucagon and pancreatic polypeptide (PP) was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on vascular resistance and exocrine secretion. Splanchnic nerve stimulation increased glucagon and PP output (2 to 3-fold) and inhibited insulin output (by 42%). Propranolol abolished the effect on PP and glucagon secretion, but did not affect the inhibition of insulin secretion. Phenoxybenzamine abolished the inhibition of insulin secretion, reduced the effect on glucagon secretion and enhanced the effect on pancreatic polypeptide secretion. Combined α- and β-adrenergic blockade abolished all effects of splanchnic nerve stimulation. Vagus nerve stimulation increased the secretion of all 3 hormones (PP: up to 30-fold, insulin and glucagon: 3 to 5-fold). The effect on insulin and PP-secretion was mimicked by acetylcholine at 10 −7−10 −6 M, whereas glucagon secretion was inhibited. The effect of vagus nerve stimulation on insulin and PP secretion was augmented by physostigmine, and inhibited (but not abolished) by atropine at 10 −7−10 −6 M. The effect on glucagon secretion was inhibited by physostigmine and unaffected by atropine. It is concluded that all of the effects of splanchnic nerve stimulation on insulin and PP secretion can be explained by interactions of norepinephrine with excitatory β-receptors on PP-cells and inhibitory receptors on the insulin cells. Both cell types are also stimulated via muscarinic cholinoceptors, but the partial atropine resistance suggests that other transmitters participate in vagal activation. The nervous regulation of glucagon secretion is complex and may involve the peptidergic innervation of the pancreatic islets.

Further evidence for a glucose-activated secretory mechanism in the jejunum of the cat.

The present study was undertaken to further test the hypothesis of a glucose-induced secretory mechanism in the jejunum of the cat (Sj ovall et al. 1983 b). The experimental design was based on the sodium dependence of active glucose uptake from the intestinal lumen. The rate of glucose uptake from a sodium-free and a sodium-containing perfusate was compared and we also investigated the effect of splanchnic nerve stimulation (SNS) on glucose absorption. The results revealed no difference in "resting" glucose uptake between the two groups. Glucose uptake from the sodium-free solution decreased on SNS whereas no such effect was seen in the sodium-containing segments. These findings can be explained by an SNS evoked inhibition of the glucose induced secretion of sodium from the crypts, which will be rate limiting for glucose uptake when no sodium is present in the perfusate. The findings are thus consistent with the concept of a glucose activated sodium secretion. Data are also presented which indicate that this secretory response is mediated by the enteric nervous system.

The effect of splanchnic nerve stimulation on blood flow distribution, villous tissue osmolality and fluid and electrolyte transport in the small intestine of the cat.

The effect of splanchnic nerve activation on intestinal fluid transport and intramural blood flow distribution was examined in the cat. Previous reports from our laboratory have demonstrated that splanchnic nerve activation increases fluid absorption. The present study was performed to elucidate the mechanisms behind this effect. The results showed an increase in net sodium and chloride transport on splanchnic nerve activation whether intestinal blood flow decreased or not. The effect on sodium transport was due to a decrease in lumen to tissue flux. The effect could not be explained by a decrease in local blood flow, as it was present despite constant blood flow in both the villous and crypt regions. No change was seen in the villous osmolality gradient on splanchnic nerve activation. On the basis of these findings, it is proposed that the in vivo effect of splanchnic nerve activation is due to a decrease in fluid and electrolyte secretion, probably occurring in the intestinal crypts.

Effects of splanchnic nerve stimulation on cardiac preload, afterload, and output in cats.

Effects of splanchnic nerve stimulation on cardiac preload, afterload, and output in cats.

The effects of splanchnic nerve stimulation on the plasma levels of serotonin and substance P in the portal vein of the cat.

The blood levels of serotonin (5-HT) and substance P (SP) in the portal vein were studied after splanchnic nerve stimulation in the cat. The portal levels of both substances were studied before, during and after splanchnic nerve stimulation. There was a twofold increase in 5-HT during stimulation whilst the SP concentration remained unchanged. These results suggest that the nervous control of the amine release into the portal stream and the mechanism that regulates the release of the polypeptide is not the same.

INHIBITION OF ADRENAL MEDULLARY CATECHOLAMINE SECRETION BY ENFLURANE I. INVESTIGATIONS IN VIVO

The effects of enflurane anesthesia on adrenal medullary catecholamine secretion and on the pressor effect of splanchnic-nerve stimulation were studied in cats given pentobarbital for basal anesthesia. Inhalation of enflurane, 1.2 and 2.2 per cent, caused dose-related inhibition of both spontaneous catecholamine release and secretion evoked by splanchnic-nerve stimulation. During inhalation of 2.2 per cent enflurane spontaneous release of epinephrine was decreased to 19 and 25 per cent, respectively, of the initial values, and the stimulated release was decreased to 30 and 15 per cent, respectively. Enflurane also inhibited the pressor effect of splanchnic-nerve stimulation, whereas that of norepinephrine was not changed significantly. These results are similar to those previously obtained with halothane and methoxyflurane. It is concluded that the decrease in catecholamine secretion caused by enflurane is in part due to a direct effect on the chromaffin cell, namely to an inhibition of the secretion-stimulating effect of acetylcholine released from splanchnic nerves.

Inhibition of Adrenal Medullary Catecholamine Secretion by Enflurane

The effects of enflurane anesthesia on adrenal medullary catecholamine secretion and on the pressor effect of splanchnic-nerve stimulation were studied in cats given pentobarbital for basal anesthesia. Inhalation of enflurane, 1.2 and 2.2 per cent, caused dose-related inhibition of both spontaneous catecholamine release and secretion evoked by splanchnic-nerve stimulation. During inhalation of 2.2 per cent enflurane spontaneous release of epinephrine was decreased to 19 and 25 per cent, respectively, of the initial values, and the stimulated release was decreased to 30 and 15 per cent, respectively. Enflurane also inhibited the pressor effect of splanchnic-nerve stimulation, whereas that of norepinephrine was not changed significantly. These results are similar to those previously obtained with halothane and methoxyflurane. It is concluded that the decrease in catecholamine secretion caused by enflurane is in part due to a direct effect on the chromaffin cell, namely to an inhibition of the secretion-stimulating effect of acetylcholine released from splanchnic nerves.

Effect of splanchnic nerve stimulation on glucagon and insulin output in the dog.

In order to study the role of the sympathetic nerves in the regulation of glucagon and insulin secretion, the distal stump of the left splanchnic nerve was electrically stimulated at the diaphragmatic level in the anesthetized dog under bilateral ligation of the adrenal veins. During stimulation, plasma glucose concentration rose rapidly, and pancreatic vein plasma concentration of glucagon increased along with pancreatic vein blood flow, indicating a greater output of glucagon. Insulin output in pancreatic vein plasma was slowly elevated despite continued stimulation. Pretreatment with propranolol resulted in a decline of the basal output of both glucagon and insulin and in their marked initial fall at the onset of the stimulus. However, glucagon output still showed a vigorous increase during neural stimulation whereas insulin output remained totally suppressed, but showed a rebound rise after cessation of stimulation. Pretreatment with phentolamine evoked an enhancement in both basal output of insulin and its response to splanchnic stimulation, but did not exert any marked effect on glucagon output. Pretreatment with atropine inhibited the basal output of glucagon and insulin, but the response of insulin output to splanchnic stimulation was not suppressed, thus excluding the possibility that activation of aberrant parasympathetic nerve fibers located in the splanchnic nerve would be responsible for the delayed increase in insulin release. The present results indicate that glucagon secretion may be regulated by different receptor mechanisms from those involved in insulin release following sympathetic activation.

Ion transport in rabbit ileal mucosa. 3. Effects of catecholamines.

Ion transport in rabbit ileal mucosa. 3. Effects of catecholamines.