Corticotropin-releasing factor inhibits gastric emptying in dogs: Studies on its mechanism of action

The effects of corticotropin-releasing factor (CRF) on gastric emptying of a saline solution was further investigated in six dogs prepared with gastric fistulas and chronic cerebroventricular guides and in four other dogs with chronic gastric fistulas and pancreatic (Herrera) cannulas. Intravenous infusion of CRF significantly inhibited gastric emptying whereas intracerebroventricular injection of CRF had no effect. Pharmacologic blockade of β-adrenergic system by propranolol did not modify intravenous CRF induced delay in gastric emptying. Intravenous CRF did not influence basal pancreatic secretion whereas secretin infused stimulated bicarbonate secretion. These results indicate that intravenous but not intracerebroventricular administration of CRF inhibited gastric emptying of a saline solution in dogs. The inhibitory effect of intravenous CRF on gastric emptying is not mediated by the β-adrenergic nervous system, and not secondary to the release of other peptides that affect both pancreatic secretion and gastric emptying such as cholecystokinin and peptide YY.     

Effects of hypo- and hyper-capnia on myocardial blood flow and metabolism during epinephrine infusion in the dog

We have previously demonstrated a 40% increase in myocardial blood flow (MBF) during hypercapnia but no significant decrease of MBF during hypocapnia. The present study was undertaken to evaluate if epinephrine infusion, which increases both myocardial oxygen consumption (MVo2) and myocardial performance, might influence the effects of hypocapnia and hypercapnia on MBF. Induction of hypocapnia was performed by hyperventilation in closed-chest dogs anesthetized with pentobarbital. By adding carbon dioxide to the inspiratory gas, normocapnia and hypercapnia were created. Epinephrine infusion (0.8 microgram X kg-1 X min-1) increased MBF and cardiac output (CO) by 90 and 140%, respectively, while MVo2 was increased by 45%. Epinephrine had a direct coronary vasodilating effect in excess of myocardial needs evidenced by increased oxygen content of the coronary sinus blood. During epinephrine infusion, induction of hypocapnia effected no change of MBF, while myocardial oxygen extraction increased significantly. Although oxygen saturation (So2) and Po2 in the coronary sinus blood decreased, these values remained well above those with hypocapnia without epinephrine infusion, thereby excluding impaired oxygen supply to the heart. Hypercapnia induced an increase of MBF by nearly 40% despite the coronary vasodilatation already induced by epinephrine infusion.     

The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.     

Epinephrine-induced decrease in repetitive extrasystole threshold is reversed by tyrosine in conscious dogs.

Previous studies indicate that availability of L-tyrosine, the precursor for catecholaminergic neurotransmitters, reduced psychological and physiological effects of stressful situations including hypotension, cold and behavioral stress. The current study examined the effect of L-tyrosine administration on cardiac vulnerability to arrhythmia induced by an infusion of epinephrine in conscious dogs. Heart rate, mean arterial pressure and cardiac electrophysiologic parameters, i.e., effective refractory period and repetitive extrasystole threshold, were measured during infusion of epinephrine (0.3 micrograms/kg/min x 30 min), before and after L-tyrosine (B mg/kg iv bolus). Epinephrine administration significantly increased heart rate by 39% (p less than 0.05), and decreased repetitive extrasystole threshold by 33% (p less than 0.05). Mean arterial pressure and effective refractory period were unchanged. Following L-tyrosine, repetitive extrasystole threshold was restored to baseline levels. Tyrosine may thus ameliorate stress-induced increases in ventricular vulnerability to arrhythmias in conscious animals.     

Inhibition of pentagastrin-stimulated gastric acid secretion by intraileal administration of bile and elevation of plasma concentrations of gut glucagon-like immunoreactivity in anesthetized dogs

The effects of intraileal administration of bile on gastric acid secretion stimulated by a submaximal dose of intravenous pentagastrin infusion and on plasma concentrations of gut glucagon-like immunoreactivity (gut GLI) were studied in anesthetized dogs. Gastric acid secretion was measured for a 2-h period at 15-min intervals before and after intraluminal instillation of test solutions. 100 ml of canine bladder bile diluted to 10% in saline evoked a significant inhibition (20%) of gastric acid secretion. The inhibition of gastric acid secretion was accompanied by an elevation of plasma concentration of gut GLI, whereas saline instillation (in controls) caused no responses. Although the inhibition of gastric acid secretion and the elevation of plasma gut GLI are parallel phenomena, gut GLI can be reasonably postulated as one of the candidate mediators of bile-induced inhibition of gastric acid secretion, since its structurally related peptides, pancreatic glucagon, glicentin and oxyntomodulin have been reported as inhibitors of gastric acid secretion.     

Development of gastric proteases in fetal pigs and pigs from birth to thirty six days of age. The effect of adrenocorticotropin (ACTH).

Development of the synthesis and secretion of gastric proteases was studied in 55 Large White x Landrace pigs from 22 days before birth (93 days gestation) to 36 days of age. The pigs came from eight litters and were 0.4 - 13.5 kg body weight. Littermate pairs were treated with either saline or adrenocorticotropin (ACTH) from three days of age. Secretion of protease activity (milk-clotting and general proteolytic activity) was investigated in anaesthetized pigs by a gastric perfusion technique using intravenous infusion of pentagastrin at dose rates of 4 and 8 micrograms/h per kg body weight. In addition, concentrations of protease zymogens (prochymosin, pepsinogen A, progastricsin) were measured in fundic tissue extracts by rocket immunoelectrophoresis. Prochymosin was present in fundic tissue at 22 days before birth, reached peak concentrations at birth and decreased in concentration during the subsequent 36 days. Pepsinogen A and progastricsin were absent or present in trace amounts in the first week after birth, but thereafter concentrations of both zymogens increased rapidly. Development of the pentagastrin-stimulated secretion of protease activity reflected the changes of zymogen concentrations in fundic tissue. Chronic treatment of pigs with ACTH from three days of age significantly increased the concentration of prochymosin in fundic tissue at 9-11 days and the concentrations of pepsinogen A and progastricsin at 34-36 days of age. Hormones such as ACTH and glucocorticoids may therefore play a regulatory role in the ontogeny of porcine gastric proteases.     

Role of histamine H2-receptors in gastric and pancreatic release of somatostatin-like immunoreactivity during the gastric phase of a meal

The present study was designed to determine the role of H₂-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 ± 540 pg/ml during a control infusion of saline and 4780 ± 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P < 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 ± 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 ± 358 pg/ml in the control experiments and 4430 ± 1024 pg/ml during cimetidine infusion (P < 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant).The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 ± 2514 pg/ml during saline was lowered to only 6728 ± 2257 pg/ml during cimetidine (ifP < 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of if5641 ± to be one regulatory component in the modulation of gastric acid secretion and gastrin release [21,26] during the gastric phase of a meal. The possible involvement of H₂-receptors in this regulatory system is schematized in Fig. 7.Pancreatic SLI release is also influenced by H₂-receptors but this appears to depend on the intragastric pH; stimulation of the receptors appears to lower the pancreatic SLI response to neutral protein and raise the response to acidified protein. If these effects are due to stimulation of gastric and/or pancreatic H₂-receptors can not be determined from the present data.These findings, in conjunction with previous studies [21–25], reveal a highly complex regulatory system for somatostin release during the gastric phase of meal, and indicate that, in addition to the influence of muscarinic-cholinergic [23], adrenergic mechanisms [24] and prostaglandins [25], reveal a histaminergic influence must now be recognized.     

Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat

Ghrelin is a gut peptide that is secreted from the stomach and stimulates food intake. There are ghrelin receptors throughout the gut and intracerebroventricular ghrelin has been shown to increase gastric acid secretion. The aim of the present study was to examine the effects of peripherally administered ghrelin on gastric emptying of a non-nutrient and nutrient liquid, as well as, basal and pentagastrin-stimulated gastric acid secretion in awake rats. In addition, gastric contractility was studied in vitro. Rats equipped with a gastric fistula were subjected to an intravenous infusion of ghrelin (10-500 pmol kg(-1) min(-1)) during saline or pentagastrin (90 pmol kg(-1) min(-1)) infusion. After administration of polyethylene glycol (PEG) 4000 with 51Cr as radioactive marker, or a liquid nutrient with (51)Cr, gastric retention was measured after a 20-min infusion of ghrelin (500 pmol kg(-1) min(-1)). In vitro isometric contractions of segments of rat gastric fundus were studied (10(-9) to 10(-6) M). Ghrelin had no effect on basal acid secretion, but at 500 pmol kg(-1) min(-1) ghrelin significantly decreased pentagastrin-stimulated acid secretion. Ghrelin had no effect on gastric emptying of the nutrient liquid, but significantly increased gastric emptying of the non-nutrient liquid. Ghrelin contracted fundus muscle strips dose-dependently (pD2 of 6.93+/-0.7). Ghrelin IV decreased plasma orexin A concentrations and increased plasma somatostatin concentrations. Plasma gastrin concentrations were unchanged during ghrelin infusion. Thus, ghrelin seems to not only effect food intake but also gastric motor and secretory function indicating a multifunctional role for ghrelin in energy homeostasis.     

The role of secretin in the control of gastric secretion and emptying in the dog

It is well established that duodenal acidification strongly inhibits gastric acid secretion, gastric emptying rate and gastrin release. These effects are at least partly mediated via hormonal pathways, but it is not known whether they are mediated by the release of one peptide named in the past enterogastrone, or by several peptides acting together. The effects of duodenal acidification on gastric acid secretion and gastrin release can be reproduced by infusion of small doses of secretin and plasma secretin levels increase during duodenal acidification or after a meal. This peptide is thus the most probable candidate as an enterogastrone. It has however never been clearly shown that administration of low doses of secretin do decrease gastric emptying rate as well as acid secretion. Experiments were performed on four dogs with gastric fistulas. A peptone solution was infused into the stomach. The experiments were repeated during infusion of synthetic secretin. Our results indicate that infusion of low doses of secretin reproduce all the effects of duodenal acidification: a significant inhibition of gastric acid secretion, gastrin release and gastric emptying rate.     

Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans

Decreased acid clearance and increased exposure to acid of the duodenum have been reported in a subset of functional dyspepsia patients. However, the mechanism by which increased duodenal acid exposure may affect symptoms is unclear. The aim of the present study was to investigate the effects of duodenal acidification on proximal gastric tone and mechanosensitivity in humans. An infusion tube with a pH electrode attached was positioned in the second part of the duodenum, and a barostat bag was located in the gastric fundus. In 12 healthy subjects, fundic tone and sensitivity to distensions were assessed before and during duodenal infusion of 0.1 N hydrochloric acid or saline in a randomized, double-blind design. In 10 healthy subjects, meal-induced accommodation was measured during duodenal infusion of acid or saline. Acid infusion in the duodenum significantly increased fundic compliance and decreased fasting fundic tone. This was accompanied by a significant decrease in the pressures and the corresponding wall tensions at the thresholds for discomfort. During infusion of acid, significantly higher perception and symptom scores were obtained for the same distending pressures. The meal-induced fundic relaxation was significantly smaller during acid infusion compared with saline infusion. In conclusion, duodenal acidification induces proximal gastric relaxation, increases sensitivity to gastric distension, and inhibits gastric accommodation to a meal. Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms.     

Gastric and cardiac organoprotection by lidocaine

The concept of cytoprotection has been applied to many tissues afforded protection by drugs or endogenous chemicals against organelle, cyto- or histopathologic damage. We review here the "organoprotection" by lidocaine in rats and dogs as appraised by in vitro, ex vivo, and in vivo experiments with the stomach and heart, and as revealed at organelle to organ functional levels. Gastric mucosal lesions induced by 80% ethanol with 100 mM HCl on the ex vivo rat stomach were significantly reduced by lidocaine (2.2-4.4 mg/kg bolus followed by 66-132 micrograms/kg/min i. v. infusion). In anesthetized dogs with gastric corporeal lesions induced by increased gastric intraluminal pressure (50 mm Hg, 2.5 hrs), lidocaine (2.2 mg/kg bolus plus 66 micrograms/kg/min infusion) significantly reduced lesion severity. In the isolated rat heart, reperfusion after a 60 min period of ischemia induced localized cardiac mitochondrial swelling and disruption in ventricular apices which was greatly reduced if hearts were pretreated (15 min perfusion with lidocaine). In intact rats subjected to hemorrhagic shock, lidocaine pretreatment also facilitated shock resuscitation and reduced ultrastructural damage. In these diverse experiments, lidocaine organoprotection was likely mediated in part through reduction of ischemia induced organelle membrane damage and through reduction of reperfusion-induced superoxide and other oxygen-derived free radical related damage.     

Epinephrine induces tissue perfusion deficit in porcine endotoxin shock: evaluation by regional CO(2) content gradients and lactate-to-pyruvate ratios

Epinephrine is widely used as a vasoconstrictor or inotrope in shock, although it may typically induce or augment lactic acidosis. Ongoing debate addresses the question of whether hyperlactatemia per se is a sign of tissue perfusion deficit or aerobic glycolysis. We wanted to test the hypothesis that epinephrine has selective detrimental effects on visceral perfusion and metabolism. We performed rigorous regional venous blood gas analyses as well as intraperitoneal microdialysis. We used a mathematical model to calculate regional arteriovenous CO(2) content gradients and estimated the magnitude of the Haldane effect in a porcine model of prolonged hypotensive shock induced by endotoxin infusion (mean arterial blood pressure < 60 mmHg). Subsequently, vasopressors (epinephrine or norepinephrine) were administered and adjusted to maintain systemic mean arterial pressure > 70 mmHg for 4 h. Epinephrine caused systemic hyperlactatemia and acidosis. Importantly, both systemic and regional venous lactate-to-pyruvate ratios increased. Epinephrine was associated with decreasing portal blood flow despite apparently maintained total splanchnic blood flow. Epinephrine increased gastric venous-to-arterial Pco(2) gradients and CO(2) content gradients with decreasing magnitude of the Haldane effect, and the regional gastric respiratory quotient remained higher after epinephrine as opposed to norepinephrine infusion. In addition, epinephrine induced intraperitoneal lactate and glycerol release. We did not observe these adverse hemodynamic or metabolic changes related to norepinephrine with the same arterial pressure goal. We conclude that high CO(2) content gradients with decreasing magnitude of the Haldane effect pinpoint the most pronounced perfusion deficiency to the gastric wall when epinephrine, as opposed to norepinephrine, is used in experimental endotoxin shock.     

Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats

We investigated the gastric acid secretory and motility responses to microinjection of thyrotropin-releasing hormone (TRH) into the dorsal motor nucleus of the vagus (DMV) in anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral and corpus contractions were continuously recorded by extraluminal force transducers. TRH dissolved in 200 nl of saline and microinjected unilaterally into the DMV induced a dose-dependent (50-200 ng) increase in gastric acid secretion. The acid secretory response began in the first 15 min collection and lasted 45 min. TRH frequently increased the force of contractions of the antrum and corpus within one minute of microinjection. The minimal effective dose for eliciting increased motility was lower than for inducing acid secretion. These results demonstrate that TRH acts in the DMV of cats to stimulate gastric acid secretion and contractions.     

Alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus.

This study tested whether alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in diabetes mellitus. Experiments were conducted in dogs instrumented with catheters in the aorta and coronary sinus and with a flow transducer around the circumflex coronary artery. Diabetes was induced with alloxan monohydrate (n = 8, 40 mg/kg i.v.). Arterial plasma glucose concentration increased from 4.7 +/- 0.2 mM in nondiabetic, control dogs (n = 8) to 21.4 +/- 1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen consumption (MVo(2)), aortic pressure, and heart rate were measured at rest and during graded treadmill exercise before and after infusion of the alpha-adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs, exercise increased MVo(2) 2.7-fold, coronary blood flow 2.2-fold, and heart rate 2.3-fold. Coronary venous Po(2) fell as MVo(2) increased during exercise. After alpha-adrenoceptor blockade, exercise increased MVo(2) 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs, alpha-adrenoceptor blockade significantly decreased the slope of the relationship between coronary venous Po(2) and MVo(2). The difference between the untreated and phentolamine-treated slopes was greater in the diabetic dogs than in the nondiabetic dogs. In addition, the decrease in coronary blood flow to intracoronary norepinephrine infusion was significantly augmented in anesthetized, open-chest, beta-adrenoceptor-blocked diabetic dogs compared with the nondiabetic dogs. These findings demonstrate that alpha-adrenoceptor-mediated coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during physiological increases in MVo(2).     

Histamine in stress ulcer prophylaxis in rats.

BACKGROUND: Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased formation of histamine leading to an increase in gastric acid secretion is accompanied with gastroprotection and acceleration of gastric ulcer healing. AIM: Of this study was to examine the effect of histamine on stress induced gastric ulcers in rats. METHODS: Male Wistar rats were exposed to water immersion and restrain stress (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole. RESULTS: WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or omeprazole caused an additional reduction in ulcer area. Gastroprotective effect of histamine was accompanied with the increase in gastric blood flow (GBF). Administration of omeprazole or ranitidine alone was without significant effect on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1beta was significantly reduced after administration of omeprazole, ranitidine, or histamine, however, the effect of histamine was less pronounced. DNA synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in combination with ranitidine or omeprazole caused an additional increase in DNA synthesis. CONCLUSIONS: Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induced gastric lesions. This effect of histamine seems to be independent on gastric acid secretion but related to the increase in gastric blood flow and the reduction in activation of cytokine cascade.     

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs

Wine apparently stimulates gastric acid secretion both in man and animals, yet the underlying mechanism remains unclear. The present study was attempted to clarify the pharmacological properties involved in gastric acid secretion stimulated by wine in beagle dogs. Commercially available red or white wine, 14% ethanol, or 10% peptone meal was intragastrically administered to dogs with vagally denervated Heidenhain pouches. Gastric acid secretion was stimulated by both red and white wines (25-50 ml) for 45-60 min. While S-0509 only tended to inhibit wine-stimulated gastric acid secretion, both atropine and famotidine significantly inhibited wine-stimulated gastric acid secretion. Plasma gastrin level was not significantly increased by administration of red and white wines. Administration of 14% ethanol also stimulated gastric acid secretion, but the effect was about half of that of wine. Combined administration of wine and peptone resulted in a biphasic stimulation of gastric acid secretion. S-0509, atropine and famotidine significantly inhibited wine+peptone meal stimulation, yet the order of inhibition of cumulative acid secretion was in the order, famotidine>atropine>S-0509. It was concluded that wine stimulated gastric acid secretion in denervated dogs via acethylcholine- and histamine-dependent mechanisms, but nearly independent from the intervention of gastrin.     

Cardiovascular effects of intravenous and intracoronary administration of atrial natriuretic peptide in halothane anesthetized dogs

Cardiovascular actions of synthetic 1-28 human natriuretic peptides (hANP) were examined in dogs anesthetized with halothane. In seven closed-chest dogs a Swan-Ganz catheter was inserted for measurement of cardiac output. Intravenous infusion of increasing doses of hANP (0.1, 0.3, 0.9 microgram/kg/min) lowered mean aortic pressure without affecting heart rate significantly. Cardiac output and pulmonary wedge pressure were markedly decreased while total peripheral resistance was increased significantly. All these parameters returned to control levels after 1 hr of recovery with an 100-150ml of saline infusion to increase pulmonary capillary wedge pressure to the preinfusion value. Intracoronary infusion of hANP (0.05 and 0.1 microgram/kg/min) did not cause any significant changes in coronary flow and regional contraction. These results indicate that the hypotensive action of hANP is due to a decrease in cardiac output mediated by reduced preload but not by negative inotropic action.     

Adrenergic control of pancreatic glucagon secretion

In order to characterize the adrenergic control of pancreatic A cell, the effect on the glucagon secretion of three sympathomimetic substances (epinephrine, isoproterenol, phenylephrine) and two adrenergic blockers (propranolol and phentolamine) have been separately examined by the isolated perfused rat pancreas. The study was performed in basal state and during glucagon hypersecretion induced by arginine or glucopenia. Epinephrine and isoproterenol infusion determined a prompt an sustained glucagon release both in the basal state and during glucagon hypersecretion. The effect of phenylephrine infusion was slight. In the presence of propranolol, glucagon secretion induced by metabolic stimulus was significantly depressed. The glucagon secretion in the same experimental conditions was insignificantly enhanced by phentolamine. Finally propranolol infusion reverse the glucagon secretion induced by phenylephrine. In conclusion the pancreatic glucagon secretion in our model of study is clearly induced by B adrenergic receptor stimulation.     

Pulmonary responses to tracheal or esophageal acidification in guinea pigs with airway inflammation.

The association between asthma and gastroesophageal reflux has been attributed to microaspiration of gastric contents and/or vagally mediated reflex bronchoconstriction. In previous experimental studies concerning the pulmonary effects of tracheal or esophageal acid infusion, only animals without airway inflammation have been studied. We assessed the effects of esophageal and tracheal administration of hydrochloric acid (HCl) on normal guinea pigs (GP) and GP with airway inflammation induced by repeated ovalbumin exposures. These GP were anesthetized (pentobarbital sodium) and received 1) 20 microl of either 0.2 N HCl or saline into the trachea, or 2) 1 ml of either 1 N HCl or saline into the esophagus. Intratracheal HCl resulted in a significant increase in both respiratory system elastance and resistance (P < 0.001). There were no significant changes in respiratory mechanics when HCl was infused into the esophagus. In conclusion, we observed that infusion of large volumes of HCl into the esophagus did not change pulmonary mechanics significantly, even in guinea pigs with chronic allergen-induced airway inflammation. In contrast, intratracheal administration of small amounts of acid had substantial effects in normal GP and GP with airway inflammation.     

Islet-activating protein (IAP)-induced adrenergic modulation of pancreatic A and B cell in dogs

Islet-activating protein (IAP) is a substance purified from the culture medium of Bordetella pertussis, and its main action is characterized by the enhancement of secretory response to glucose and other stimuli in pancreatic islet. In this experiment, the effect of IAP on epinephrine-induced secretion of immunoreactive insulin (IRI) and glucagon (IRG) was investigated in normal dogs. Epinephrine suppressed IRI secretion and it had a little increment to IRG secretion in control group, while IRI and IRG secretions were significantly increased by epinephrine in IAP pretreated group. Using beta-blocker (Propranolol) with epinephrine, these increments of IRI and IRG secretions in IAP pretreated group were abolished. However, using alpha-blocker (Phentolamine) with epinephrine, these secretions of IRI and IRG in IAP pretreated group were much more increased than epinephrine alone induced secretions. Blood glucose levels were lower in IAP pretreated group than in control group throughout the loading tests in all of the experiments. These findings suggest that (1) IAP decreases blood glucose level and (2) IAP enhances epinephrine-induced secretion of insulin and glucagon by acceleration of beta-adrenergic effect and by reduction of alpha-adrenergic suppression in dogs.