Decrease In Intragastric Pressure Research Articles

Evaluation of a novel technique involving ultrasound-guided, temporary, percutaneous gastropexy and gastrostomy catheter placement for providing sustained gastric decompression in dogs with gastric dilatation-volvulus.

To evaluate the feasibility of ultrasound-guided, temporary, percutaneous T-fastener gastropexy (TG) and gastrostomy catheter (GC) placement for providing sustained gastric decompression in dogs with acute gastric dilatation-volvulus (GDV) and to compare findings with those of trocarization. 16 dogs with GDV. Dogs were randomly assigned to undergo gastric decompression by means of percutaneous trocarization (trocar group; n = 8) or temporary TG and GC placement (TTG+GC group; 8) with ultrasound guidance. The gastric volvulus was then surgically corrected, and the decompression sites were examined. Outcomes were compared between groups. The proportion of dogs with successful decompression did not differ significantly between the TTG+GC (6/8) and trocar (7/8) groups; median procedure duration was 3.3 and 3.7 minutes, respectively. After the failed attempts in the TTG+GC group, the procedure was modified to include ultrasound guidance during T-fastener placement. The decrease in intragastric pressure by 5 minutes after trocar or GC insertion was similar between groups. For dogs in the TTG+GC group, no significant difference in intragastric pressure was identified between 5 and 60 minutes after GC insertion. Complications included inadvertent splenic or jejunal placement in 2 dogs (TTG+GC group) and malpositioned and ineffective trocar placement in 1 dog (trocar group). All dogs survived for at least 2 weeks. Ultrasound-guided, temporary, percutaneous TG and GC placement was safe and effective at providing sustained gastric decompression in dogs with GDV, suggesting that this technique would be ideal for dogs in which surgical delays are anticipated or unavoidable.

Temporary percutaneous T-fastener gastropexy and continuous decompressive gastrostomy in dogs with experimentally induced gastric dilatation.

OBJECTIVE To evaluate a percutaneous, continuous gastric decompression technique for dogs involving a temporary T-fastener gastropexy and self-retaining decompression catheter. ANIMALS 6 healthy male large-breed dogs. PROCEDURES Dogs were anesthetized and positioned in dorsal recumbency with slight left-lateral obliquity. The gastric lumen was insufflated endoscopically until tympany was evident. Three T-fasteners were placed percutaneously into the gastric lumen via the right lateral aspect of the abdomen, caudal to the 13th rib and lateral to the rectus abdominis muscle. Through the center of the T-fasteners, a 5F locking pigtail catheter was inserted into the gastric lumen and attached to a device measuring gas outflow and intragastric pressure. The stomach was insufflated to 23 mm Hg, air was allowed to passively drain from the catheter until intraluminal pressure reached 5 mm Hg for 3 cycles, and the catheter was removed. Dogs were hospitalized and monitored for 72 hours. RESULTS Mean ± SD catheter placement time was 3.3 ± 0.5 minutes. Mean intervals from catheter placement to a ≥ 50% decrease in intragastric pressure and to ≤ 6 mm Hg were 2.1 ± 1.3 minutes and 8.4 ± 5.1 minutes, respectively. After catheter removal, no gas or fluid leakage at the catheter site was visible laparoscopically or endoscopically. All dogs were clinically normal 72 hours after surgery. CONCLUSIONS AND CLINICAL RELEVANCE The described technique was performed rapidly and provided continuous gastric decompression with no evidence of postoperative leakage in healthy dogs. Investigation is warranted to evaluate its effectiveness in dogs with gastric dilatation-volvulus.

Secretin‐induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways

Secretin has been shown to delay gastric emptying and inhibit gastric motility. We have demonstrated that secretin acts on the afferent vagal pathway to induce gastric relaxation in the rat. However, the efferent pathway that mediates the action of secretin on gastric motility remains unknown. We recorded the response of intragastric pressure to graded doses of secretin administered intravenously to anaesthetized rats using a balloon attached to a catheter and placed in the body of the stomach. Secretin evoked a dose-dependent decrease in intragastric pressure. The threshold dose of secretin was 1.4 pmol kg(-1) h(-1) and the effective dose, 50% was 5.6 pmol kg(-1) h(-1). Pretreatment with hexamethonium markedly reduced gastric relaxation induced by secretin (5.6 pmol kg(-1) h(-1)). Bilateral vagotomy also significantly reduced gastric motor responses to secretin. Administration of N(G)-nitro-L-arginine methyl ester (10 mg kg(-1)) did not affect gastric relaxation induced by secretin. In contrast, intravenous administration of a vasoactive intestinal polypeptide (VIP) antagonist (30 nmol kg(-1)) reduced the gastric relaxation response to secretin (5.6 pmol kg(-1) h(-1)) by 89 +/- 5%. Indomethacin (2 mg kg(-1)) reduced gastric relaxation induced by secretin (5.6 pmol kg(-1) h(-1)) by 87 +/- 5%. Administration of prostaglandin (48 mg kg(-1) h(-1)) prevented this inhibitory effect. Indomethacin also reduced gastric relaxation induced by VIP (300 pmol kg(-1)) by 90 +/- 7%. These observations indicate that secretin acts through stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. Through nicotinic synapses, secretin stimulates VIP release from postganglionic neurons in the gastric myenteric plexus, which in turn induces gastric relaxation through a prostaglandin-dependent pathway.

Comments on “Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine”

The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 ± 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 ± 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), NG-nitro-l-arginine methyl ester microinjected into the NTS ( n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, α2-adrenergic blockers microinjected into the DMV ( n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.

Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine

The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 +/- 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 +/- 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), N(G)-nitro-L-arginine methyl ester microinjected into the NTS (n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, alpha2-adrenergic blockers microinjected into the DMV (n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.

Mesenteric lymph collected during peritonitis or sepsis potently inhibits gastric motility in rats.

Gastrointestinal motility is strongly inhibited during peritonitis or sepsis and proinflammatory cytokines released into mesenteric lymph during an acute gastrointestinal insult mediate systemic responses. We investigated whether mesenteric lymph collected during peritonitis or sepsis inhibits gastric motility and gastric emptying. Mesenteric lymph was collected for 12 hours from three experimental groups: vehicle (saline, 1 ml, intraperitoneally [ip], control lymph), peritonitis (0.5% acetic acid, 1 ml, ip, peritonitis lymph), and sepsis (lipopolysaccharide [LPS], 5 mg/kg, 1 ml, ip, sepsis lymph). Gastric motility and gastric emptying were measured in recipient rats in response to lymph injections into the jugular vein. Quantitative polymerase chain reaction (PCR) for tumor necrosis factor alpha (TNFalpha) gene expression in the jejunum and in lymph cells were measured during sepsis. Mesenteric lymph flow significantly increased during peritonitis or sepsis (lymph flow [ml] per 60 minutes; control 2.45 +/- 0.04; peritonitis 2.67 +/- 0.07; sepsis 3.25 +/- 0.1, p < 0.01 vs. control). Injection of peritonitis or sepsis lymph (1 ml) produced a significant and prolonged inhibition of gastric motility in recipient rats (decrease in intragastric pressure and duration: control lymph -0.14 +/- 0.05 cm H(2)O, 1.89 +/- 1.31 minutes; peritonitis lymph: -0.56 +/- 0.06 cm H(2)O, 9.9 +/- 0.9 minutes; sepsis lymph: -0.51 +/- 0.05 cm H(2)O, 6.9 +/- 0.6 minutes; p < 0.001 vs. control for all comparisons). Gastric emptying was significantly inhibited by continuous infusion of sepsis lymph (3 ml per 60 minutes; gastric emptying: saline 81% +/- 4%; control lymph: 80% +/- 6%; sepsis lymph: 44% +/- 10%; p < 0.001 vs. control). TNFalpha gene expression in the gut wall of the jejunum increased during sepsis over 90-fold within the first 2 hours and decreased continuously thereafter (relative TNFalpha mRNA transcription: basal 1.0 +/- 0.05; LPS 2 hours: 91.9 +/- 2.6, p < 0.001 vs. basal; 12 hours: 24.7 +/- 16.8, not significant [NS]; 24 hours: 7.0 +/- 3.4, NS). In conclusion, mediators in mesenteric lymph, possibly cytokines, may be responsible for the inhibition of gastric motility during peritonitis or sepsis. Because the composition of mesenteric lymph probably reflects the interstitial fluid of the gut wall, monitoring visceral lymph might be an extremely beneficial tool to determine mediators released during impaired gut wall function.

Excitation of dorsal motor vagal neurons evokes non-nicotinic receptor-mediated gastric relaxation

Vagal stimulation results in both gastric motor excitatory and non-adrenergic non-cholinergic (NANC) inhibitory responses. The NANC pathway involves preganglionic cholinergic neurons, which act through nicotinic receptors to ultimately evoke gastric smooth muscle relaxation via release of nitric oxide (NO) and other neurotransmitters. Within the dorsal motor nucleus of the vagus (DMN), some preganglionic neurons also contain NO synthase. The NO synthase-containing neurons innervate the gastric fundus where adaptive relaxation occurs. This study tests the hypothesis that chemical stimulation of vagal motor neurons in animals, in which nicotinic receptors are blocked, evokes an NO-dependent gastric relaxation. A cell body excitant, N-methyl- d-aspartate (NMDA, 0.03–3 nmol), was microinjected into the DMN in anesthetized rats while recording intragastric pressure (IgP). The first group received NMDA before and after administration of a ganglionic blocker, hexamethonium bromide (15 mg/kg, i.v.) and atropine (1.0 mg/kg). Significant dose-dependent increases in IgP and gastric motility occurred before hexamethonium after the 0.3 and 3 nmol doses of NMDA. After hexamethonium, 0.3 and 3 nmol NMDA evoked significant decreases in IgP. A second group of rats was hexamethonium-pretreated and received NMDA microinjection into the DMN before and after an NO synthase inhibitor, N G-nitro- l-arginine methyl ester (10 mg/kg, i.v.). The NMDA-evoked decrease in IgP was completely abolished by the NO synthase inhibitor. These data support the novel idea that NO synthase-containing preganglionic neurons mediate gastric relaxation that is independent of nicotinic receptors.

Duodenal acid-induced gastric relaxation is mediated by multiple pathways.

In this study, we used an in vivo anesthetized rat model to investigate the mechanisms responsible for duodenal acid-induced inhibition of gastric motility. Intraduodenal infusion of HCl produced a rate-dependent decrease in intragastric pressure. Infusion of HCl at 2 ml/h produced a physiological plasma secretin level and elicited a decrease in intragastric pressure of 3.0 +/- 0. 2 cmH20. Infusion of rabbit secretin antiserum reduced the acid-induced inhibition of gastric motility by 85 +/- 5%, suggesting mediation mainly by endogenous secretin. Administration of the cholecystokinin (CCK)-A antagonist MK-329 caused only a modest 10 +/- 3% reduction in gastric relaxation, whereas the serotonin antagonist ICS-205930 had no effect. In contrast, immunoneutralization with the secretin antibody caused only a 15% reduction in the relaxation evoked by a higher rate of HCl infusion (3 ml/h), whereas MK-329 and ICS-205930 caused a 20 +/- 4% reduction and no reduction, respectively. Bilateral truncal vagotomy or perivagal application of capsaicin completely abolished gastric relaxation in response to low rates (1-2 ml/h) of 0.1 N HCl infusion but only partially affected gastric relaxation in response to a higher infusion rate (3 ml/h). These observations indicate that multiple pathways mediate the duodenal acid-induced inhibition of gastric motility. At low rates of HCl infusion, gastric relaxation is mediated primarily by endogenous secretin, which acts through vagal afferent pathways. At higher rates of HCl infusion, gastric relaxation is mediated by endogenous secretin, CCK, and possibly by the direct action of HCl on vagal afferent pathways or yet unidentified neuropathways.

Δ 9-Tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB 1 receptors

We investigated involvement of the autonomic nervous system in gastric motor and cardiovascular responses to Δ 9-tetrahydrocannabinol (Δ 9-THC) in anesthetized rats. Intravenously administered Δ 9-THC evoked long-lasting decreases in intragastric pressure and pyloric contractility, bradycardia, and hypotension. The changes in gastric motor function and bradycardia were abolished by vagotomy and ganglionic blockade, whereas spinal cord transection prevented the hypotensive response. Administered intravenously alone, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, a putative cannabinoid CB 1 receptor antagonist, evoked transient decrease in intragastric pressure, and hypertension that was associated with bradycardia. However, this agent completely blocked the gastric motor and cardiovascular responses to intravenous Δ 9-THC. Application of Δ 9-THC to the dorsal surface of the medulla resulted in small and short-lasting decreases in gastric motor and cardiovascular function. We conclude that the decrease in gastric motor function and bradycardia are partially due to an action of Δ 9-THC in the dorsal medulla and that intact vagal nerves are required. The hypotension was mediated through sympathetic pathways. Both gastric motor and cardiovascular effects of peripherally administered Δ 9-THC seem to be mediated through cannabinoid CB 1 receptors.

Substance P and serotonin independently affect intragastric pressure when microinjected into the nucleus raphe obscurus of the rat

We have recently shown that microinjection of substance P (SP) into the nucleus raphe obscurus (NRO) of the rat decreases intragastric pressure, whereas microinjection of serotonin (5-HT) increases it. The purpose of the present study was to investigate whether there exists a functional interaction between SP and 5-HT in the NRO of the rat in their effects on gastric motor function. This was accomplished by microinjection of SP (135 pmol) and 5-HT (0.6 and 6 nmol) into the NRO in a rapid, sequential order in α-chloralose-anesthetized rats, while monitoring intragastric pressure and pyloric and greater curvature motilities. Substance P evoked significant decreases in intragastric pressure when microinjected into the NRO after vehicle and after 5-HT (at both 0.6 and 6 nmol). There was no difference in the magnitude of the SP effect after 5-HT when compared to the response after vehicle. Serotonin at a dose of 6 nmol, but not at a dose of 0.6 nmol, elicited significant increases in intragastric pressure when microinjected after vehicle or after SP, and there was no difference between the responses to 5-HT with respect to the initial treatment. We conclude that SP and 5-HT act independently in the NRO of the rat to affect intragastric pressure.

TRH and substance P independently affect gastric motility in nucleus raphe obscurus of the rat.

The purpose of this study was to investigate whether there exists a functional interaction between thyrotropin-releasing hormone (TRH) and substance P (SP) in the nucleus raphe obscurus (NRO) in their effects on gastric motor function. This was accomplished by microinjection of TRH (6-45 pmol) and SP (10 and 135 pmol) into the NRO alone and then either as a mixture or in rapid sequential order in alpha-chloralose-anesthetized rats, while intragastric pressure and pyloric and greater curvature motility were monitored. TRH (15 and 45 pmol) evoked significant increases in gastric motor activity, whereas SP (135 pmol) elicited decreases in intragastric pressure. SP at a dose of 10 pmol was ineffective alone in altering gastric motor function. Microinjection of a mixture of TRH (15 pmol) and SP (10 pmol) into the NRO resulted in significant increases in intragastric pressure, pyloric motility, and greater curvature motility; these changes in gastric motor function were similar to the effect of TRH (15 pmol) alone. A mixture of TRH (15 pmol) and SP (135 pmol) resulted in changes in gastric motor activity that were significantly less than the effect of TRH (15 pmol) microinjected into the NRO alone and appeared to be an additive effect of each peptide. The results of sequential microinjections of both peptides were consistent with these findings. The stimulative effect of TRH (15 and 45 pmol) on intragastric pressure, microinjected into the NRO 30 s after SP (135 pmol), did not differ from the effect of TRH microinjected at the same doses after vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of NG-nitro-L-arginine methyl ester on vagally induced gastric relaxation in the anaesthetized rat.

1. The influence of the nitric oxide (NO) biosynthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the gastric relaxation induced by peripheral vagal stimulation was investigated in the anaesthetized rat. 2. Peripheral vagal stimulation (10 Hz, 10 V, 1 ms for 20 s) induced a reproducible biphasic response: a short-lasting increase followed by a more pronounced decrease in intragastric pressure. This response also occurred in reserpinized animals (5 mg kg-1, i.p., 24 h before the experiment) while atropine (1 mg kg-1, i.v.) abolished the initial increase in intragastric pressure. 3. L-NAME (1-30 mg kg-1, i.v.) induced an increase in arterial blood pressure. L-NAME (1 mg kg-1, i.v.) had no influence on the vagally induced gastric response while L-NAME (10 and 30 mg kg-1 i.v.) significantly changed it: the initial increase in intragastric pressure was enhanced while the decrease in intragastric pressure was reduced or abolished. NG-nitro-L-arginine (L-NNA, 10 mg kg-1, i.v.) had the same effect. 4. An i.v. infusion of phenylephrine (10 micrograms kg-1 min-1) inducing a pressor response similar to that produced by L-NAME (30 mg kg-1, i.v.) did not influence the vagal gastric response. Infusion of L-arginine (300 mg kg-1 bolus, then 100 mg kg-1 h-1) starting 30 min beforehand, reduced the pressor effect and prevented the influence of L-NAME (10 mg kg-1, i.v.) on the vagal gastric response. Infusion of L-arginine (300mgkg-' bolus, then lOOmgkg-lh-') starting 30min beforehand, reduced the pressor effect and prevented the influence of L-NAME (lOmgkg-,i.v.) on the vagal gastric response. After injection of both atropine (lmgkg-', i.v.) and L-NAME (30mgkg-', i.v.), the vagally induced decrease in intragastric pressure was similar to that obtained under control conditions.5. These results are consistent with NO being released and inducing gastric relaxation during peripheral vagal stimulation. In addition to NO, another inhibitory non-adrenergic non-cholinergic neurotransmitter is released.

Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats

The pathway by which cholecystokinin octapeptide (CCK-8) inhibits motility of the proximal stomach and the role of this pathway in the CCK-induced delay in gastric emptying of a liquid meal has been studied in rats by selective destruction of vagal afferent C-fibers using bilateral perineural application of the sensory neurotoxin, capsaicin, 3 or 4 days prior to the experiment. The capsaicin treatment significantly attenuated the decrease in intragastric pressure in urethan-anesthetized rats in response to CCK-8 (0.1-100 pmol iv) compared with vehicle-treated controls. Removal of the celiac-superior mesenteric ganglion completely abolished the inhibitory action of CCK-8 on gastric motility in these rats. In contrast, only celiac ganglionectomy in combination with vagotomy abolished the CCK-8 effect in vehicle-treated controls. Intravenous injection of CCK-8 (300 pmol) 5 min before intragastric administration of a methylcellulose solution decreased gastric emptying by 55% in conscious control or vehicle-treated rats. Perivagal capsaicin treatment abolished the delay in gastric emptying induced by CCK-8. In addition, capsaicin treatment alone significantly increased gastric emptying. These results demonstrate that CCK-8 decreases gastric motility in the gastric corpus and delays gastric emptying by a capsaicin-sensitive vagal afferent pathway. These same afferent fibers may also play a physiological role in the gastric emptying of liquids.

Gastric relaxation prior to enteral feeding.

The purpose of this investigation was to determine whether the observed gastric relaxation associated with the intragastric infusion of a liquid meal could be conditioned to the temporarily associated auditory cues to enteral feeding and thus produce decreased intragastric pressures under "sham" feeding conditions. Eight normal volunteers received either enteral feedings or sham feedings followed by enteral feedings on 72 separate trial days. The feedings were administered at a constant rate via a Harvard infusion pump. Intragastric pressure changes were monitored by an open tipped pressure cannula which was attached to the feeding tube. A sham feeding consisted of carrying out all preparatory procedures including activation of the feeding pump which was visually screened from the patient. Without the subjects' knowledge the liquid diet was diverted to another reservoir instead of through the nasogastric tube. This sham type infusion produced a gastric response similar to the response to a normal diet infusion as evidenced by a decrease in intragastric pressure and a suppression of irregular high amplitude contractions that are associated with hunger. This anticipatory response to enteral feeding indicative of prospective relaxation of the stomach may enhance the subsequent accommodation to a volume of diet. Additional studies are needed to investigate the importance of visual and auditory cues on patient tolerance of enteral feedings.

Dopamine as A Possible Neurotransmitter in Gastric Relaxation

In dogs with gastric fistulas, intragastric pressure was measured with a flaccid ballon containing 500 ml of water. Graded doses of dopamine caused graded decreases in intragastric pressure. The effect was blocked by pimozide or by metoclopramide but was not significantly affected by phenoxybenzamine, propranolol, guanethidine, or FLA-63 (a beta-hydroxylase inhibitor). Pretreatment with metoclopramide or with pimozide shifted the volume-pressure diagram of the stomach to the left; that is, at any given volume the pressure was greater after than before these drugs. In dogs with vagally innervated gastric pouches and gastric fistulas, feeding for 1 min (while allowing the food to leave the stomach through the gastric fistula) caused a prompt decrease in pressure in the pouch that lasted for about 5 min. Pretreatment with metoclopramide decreased the magnitude and duration of this receptive relaxation. It is concluded that these findings are consistent with (but do not establish) the hypothesis that dopamine is the neurotransmitter for receptive relaxation of the stomach, because dopamine mimics receptive relaxation, and dopamine antagonists partially block reflexly induced receptive relaxation.

Effect of Intestinal Hormones and Peptides on Intragastric Pressure in Dogs

Intragastric pressure was measured in dogs with gastric fistulas by using a flaccid balloon containing 500 ml of water. Intravenous infusion of cholecystokinin (20% pure), the carboxyl-terminal octapeptide of cholecystokinin, secretin, and vasoactive intestinal peptide produced dose-related decreases in intragastric pressure with maximal decreases of 40% or more. Glucagon and gastric inhibitory peptide produced smaller decreases in intragastric pressure. Motilin caused a dose-related increase in intragastric pressure that lasted only about 7 min despite continuing infusion of the peptide. The half-dose of cholecystokinin or of octapeptide of cholecystokinin for pancreatic protein secretion and the half-dose of secretin for pancreatic bicarbonate secretion each produced significant inhibition of intragastric pressure, suggesting that these hormones play a physiological reole in regulating gastric pressure.

Effect of Pentagastrin and Caerulein on Intragastric Pressure in the Dog

When gastric acid was not neutralized, doses of pentagastrin as small as 1 mug kg-1 hr-1 decreased intragastric pressure in dogs. When gastric acid was neutralized the smallest effective dose of pentagastrin was 8 mug kg-1 hr-1 which is 16 times the D50 for acid secretion. Thus the decrease in intragastric pressure by small doses of pentagastrin is mediated at least in part by acid secretion. Even with gastric neutralization, a dose of caerulein as small as 63 ng kg-1 hr-1, which is the D50 for pancreatic protein secretion, decreased intragastric pressure. These findings support the view that inhibition of gastric pressure occurs with physiological doses of the cholecystokinin-like peptide caerulein but only with pharmacological doses of pentagastrin.