Gastric Mucosal Blood Flow Response Research Articles

Effect of Elevated Intracranial Pressure on Gastric Acid Secretion, Mucosal Blood Flow and Mucosal Injury

Head injury is frequently accompanied by an increase in intracranial pressure and gastric lesion formation. We used a model of controlled intracranial pressure to investigate the effect of elevated intracranial pressure on gastric acid secretion and mucosal blood flow and on the susceptibility of the gastric mucosa to lesion formation. With increasing intracranial pressure, there was a corresponding increase in gastric acid output but no significant change in gastric mucosal blood flow. This imbalance between acid secretion and blood flow could be a factor in the pathogenesis of the gastric lesions seen with head injury. Susceptibility to gastric mucosal injury then was studied in a model that is independent of the acid secretory state-exogenous intragastric HCl plus ethanol. Elevated intracranial pressure did render the gastric mucosa more susceptible to injury in this model, but there was no impairment of the increased gastric mucosal blood flow response to the increased acid back-diffusion. In this situation, factors other than altered overall blood flow appear to be responsible for the increased lesion formation.

Effect of capsaicin on gastric mucosal injury and blood flow following bile acid exposure

Topical bile acid at low pH stimulates gastric mucosal blood flow (GMBF), thereby limiting injury to surface epithelial cells (SEC). Capsaicin-sensitive afferent neurons (ASN) are possible mediators of the GMBF response and, therefore, of mucosal protection. In order to investigate the effect of topical capsaicin (ASN stimulant) and topical lidocaine (ASN inhibitor) on SEC exfoliation and GMBF, vascularized wedges of canine gastric corpus were mounted in lucite chambers. Mucosae were pretreated for 15 min with saline (NSS), 160 μ M capsaicin (CAP), 4% lidocaine (LIDO), or CAP and LIDO, followed by a 30-min exposure to acid test solution (ATS; pH 1.2). The same mucosae were then pretreated in an identical fashion followed by a second 30-min exposure to 5 m M taurocholate (5 TC; pH 1.2). Parameters evaluated during both ATS and 5 TC periods were the luminal accumulation of DNA (DNAE, a sensitive marker of SEC exfoliation) and GMBF measured using radiolabeled microspheres. It was found that, relative to NSS pretreatment, CAP pretreatment increased GMBF and decreased DNAE during exposure to both ATS and 5 TC. LIDO blocked the CAP effect on GMBF but not on DNAE. Thus, ASN stimulation by CAP enhances GMBF and is protective. ANS inhibition blocks CAP's GMBF increase but not its protective capabilities. Therefore, augmentation of GMBF is not the only mechanism by which ASNs blunt SEC exfoliation.

Induction of gastric lesions by 2-deoxy-D-glucose in rats following chemical ablation of capsaicin-sensitive sensory neurons.

Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification.

Induction of Gastric Lesions by 2-Deoxy-D-Glucose in Rats Following Chemical Ablation of Capsaicin-Sensitive Sensory Neurons

Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification.

O-219 - Role of luminal H+ in gastric mucosal blood flow response during acid secretion by histamine in rats

O-219 - Role of luminal H+ in gastric mucosal blood flow response during acid secretion by histamine in rats

Effect of elevated intracranial pressure on gastric acid secretion, mucosal blood flow and mucosal injury

Head injury is frequently accompanied by an increase in intracranial pressure and gastric lesion formation. We used a model of controlled intracranial pressure to investigate the effect of elevated intracranial pressure on gastric acid secretion and mucosal blood flow and on the susceptibility of the gastric mucosa to lesion formation. With increasing intracranial pressure, there was a corresponding increase in gastric acid output but no significant change in gastric mucosal blood flow. This imbalance between acid secretion and blood flow could be a factor in the pathogenesis of the gastric lesions seen with head injury. Susceptibility to gastric mucosal injury then was studied in a model that is independent of the acid secretory state--exogenous intragastric HCl plus ethanol. Elevated intracranial pressure did render the gastric mucosa more susceptible to injury in this model, but there was no impairment of the increased gastric mucosal blood flow response to the increased acid back-diffusion. In this situation, factors other than altered overall blood flow appear to be responsible for the increased lesion formation.

Characterization of Gastric Mucosal Blood Flow Response Induced by Intragastric Capsaicin in Rats

Gastric mucosal blood flow (GMBF) was measured in the ex vivo stomachs of anesthetized rats simultaneously with mean arterial blood pressure (MBP), luminal pH and transmucosal potential difference (PD) in an attempt to characterize these responses induced by capsaicin. The stomach was mounted on a Lucite chamber, perfused with saline at the flow rate of 1 ml/min, and GMBF was measured by Laser flowmetry. Under these conditions, the pH, PD and GMBF were 3.5 to 4.0, -30 to -35 mV and 8-12 ml/min/100 g, respectively. Mucosal application of capsaicin (0.03 - 1 mg/ml for 10 min) increased GMBF in a concentration-dependent manner, without any change in PD, pH and MBP. The increased GMBF response caused by capsaicin was abolished by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg), significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.) or ruthenium red (300 micrograms/kg, i.v.), but was not affected by spantide (100 micrograms/kg, i.v.), atropine (300 micrograms/kg, i.p.) or disodium cromoglycate (30 mg/kg, i.p.). In addition, when the mucosa was exposed to capsaicin repeatedly, this response showed a marked tachyphylaxis at a high concentration (6 mg/ml). These results suggest that intragastric capsaicin increased GMBF selectively through capsaicin-sensitive sensory neurons, and this action may involve endogenous prostaglandins.

Capsaicin-Sensitive Afferent Neurons in Adaptive Responses of the Rat Stomach Induced by a Mild Irritant

Exposure of rat stomach to 1 M NaCl reduced the transmucosal potential difference (PD) followed by an increase of luminal pH and gastric mucosal blood flow (GMBF). Desensitization of capsaicin-sensitive afferent neurons significantly mitigated the increase in GMBF without affecting PD and pH responses. Mucosal application of capsaicin increased GMBF with no effect on PD and pH. The findings suggest that capsaicin-sensitive afferent neurons may be involved in the regulatory mechanism of GMBF responses induced by a mild irritant.

Capsaicin-sensitive afferent neurons in adaptive responses of the rat stomach induced by a mild irritant.

Exposure of rat stomach to 1 M NaCl reduced the transmucosal potential difference (PD) followed by an increase of luminal pH and gastric mucosal blood flow (GMBF). Desensitization of capsaicin-sensitive afferent neurons significantly mitigated the increase in GMBF without affecting PD and pH responses. Mucosal application of capsaicin increased GMBF with no effect on PD and pH. The findings suggest that capsaicin-sensitive afferent neurons may be involved in the regulatory mechanism of GMBF responses induced by a mild irritant.

Capsaicin-sensitive afferent fibers contribute to gastric mucosal blood flow response to electrical vagal stimulation

Electrical stimulation of the peripheral vagus produces a noncholinergic increase in gastric mucosal blood flow (GMBF) via unknown mechanisms. The purpose of this study was 1) to investigate whether a portion of the increase in GMBF during prolonged electrical vagal stimulation involves a mechanism separate from augmented acid secretion and 2) to determine whether antidromic activation of afferent fibers contributes to the vascular or secretory responses to electrical vagal stimulation. Electrical vagal stimulation (40 V, 6 Hz, 2 ms) applied for 30 min to the distal cut end of the subdiaphragmatic ventral vagus significantly increased gastric acid secretion and GMBF measured by hydrogen gas clearance. Atropine (0.15 mg/kg iv) or omeprazole (10 mumol/kg iv) completely abolished the secretory response to electrical vagal stimulation, while a significant increase in GMBF remained. Pretreatment with perineural application of the sensory neurotoxin capsaicin to both cervical vagi significantly reduced by 48% the increase in GMBF but not gastric acid secretion; atropine completely abolished the remaining vascular response in capsaicin-treated rats. These results suggest that prolonged electrical vagal stimulation induces a sustained increase in GMBF partially independent of augmented acid secretion and that the noncholinergic portion of the vascular response is mediated by capsaicin-sensitive vagal afferent fibers.

P-074 - Measurement of gastric mucosal blood flow responses to vasoactive drugs using cross thermocouple and H2 gas clearance methods in comparison with their blood pressure responses in rats

P-074 - Measurement of gastric mucosal blood flow responses to vasoactive drugs using cross thermocouple and H2 gas clearance methods in comparison with their blood pressure responses in rats

Gastric Mucosal Blood Flow Response to Stimulation and Inhibition of Gastric Acid Secretion

The effect of stimulation (with graded doses of intravenous pentagastrin) and inhibition (with an H2-blocker or a proton pump inhibitor) of acid secretion on corpus mucosal blood flow was investigated. Hydrogen gas clearance was used to measure blood flow in the basal portion of the mucosa of anesthetized rats. A dose-related increase in acid output increments above resting level was observed with the doses of pentagastrin from 0 (saline infusion) to 40 μg/kg ± h. With the doses of pentagastrin from 0 to 80 μg/kg ± h there was a dose-related increase in mucosal blood flow increments above resting levels. A linear correlation (r = 0.7) was observed between increments in acid output and increments in mucosal blood flow with increasing doses of pentagastrin from 0 to that producing maximal acid secretion (40 μg/kg ± h). Inhibition of pentagastrin-stimulated acid secretion by cimetidine or omeprazole returned stimulated gastric mucosal blood flow to baseline levels.