0000000000530929
AUTHOR
Brendan J.r. Whittle
Nitric oxide and sensory afferent neurones modulate the protective effects of low-dose endotoxin on rat gastric mucosal damage
Pretreatment (1 h) with low doses (5-40 micrograms/kg i.p.) of Escherichia coli endotoxin dose dependently reduced the gastric mucosal damage induced by a 10 min challenge with 1 ml ethanol (50% and 100%) in conscious rats. Treatment with the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 5 and 10 mg/kg i.p.), significantly inhibited the protective effects of endotoxin (40 micrograms/kg i.p.). The actions of L-NAME were reversed by the prior administration of L-arginine (100 mg/kg i.p.). The protective effects of endotoxin were not influenced by pretreatment with dexamethasone (5 mg/kg s.c. twice) or indomethacin (5 mg/kg s.c.). However, ablation of sensory affe…
Inhibition of gastric acid secretion by stress: A protective reflex mediated by cerebral nitric oxide
Moderate somatic stress inhibits gastric acid secretion. We have investigated the role of endogenously released NO in this phenomenon. Elevation of body temperature by 3°C or a reduction of 35 mmHg (1 mmHg = 133 Pa) in blood pressure for 10 min produced a rapid and long-lasting reduction of distension-stimulated acid secretion in the rat perfused stomach in vivo . A similar inhibitory effect on acid secretion was produced by the intracisternal (i.c.) administration of oxytocin, a peptide known to be released during stress. Intracisternal administration of the NO-synthase inhibitor, N G -nitro- l -arginine methyl ester ( l -NAME) reversed the antisecretory effect induced by all these stimul…
Endotoxin inhibition of distension-stimulated gastric acid secretion in rat: mediation by NO in the central nervous system
1. The involvement of nitric oxide in the acute inhibitory effects of low doses of endotoxin, following intracerebroventricular (i.c.v.) or intravenous (i.v.) administration, on gastric acid secretion stimulated by distension or i.v. infusion of pentagastrin has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. The i.c.v. administration of E. coli endotoxin (800 ng kg-1) abolished the acid secretory response induced by gastric distension (20 cm water intragastric pressure) within 30 min of administration. 3. By contrast, submaximal rates of acid secretion induced by i.v. infusion of pentagastrin (8 micrograms kg-1 h-1) were not inhibited by i.c.v. administr…
Modulation by opioids and by afferent sensory neurones of prostanoid protection of the rat gastric mucosa.
1. Pretreatment with capsaicin, to deplete sensory neuropeptides from primary afferent neurones or the administration of morphine (9 mg kg-1, i.v.), which can inhibit neuropeptide release, augmented gastric mucosal injury induced by a 5 min challenge with intragastric ethanol in the rat, as assessed by macroscopic and histological evaluation. 2. Morphine administration substantially attenuated the protective actions of the prostaglandin analogue 16,16 dimethyl prostaglandin E2 (dm PGE2; 0.5-20 micrograms kg-1, p.o.) against ethanol-induced damage. This reduced degree of protection by dmPGE2 was not however, the consequence of the enhanced level of damage. 3. These actions of morphine in red…
Involvement of endogenous nitric oxide in the inhibition by endotoxin and interleukin-1 beta of gastric acid secretion.
Administration of Escherichia coli endotoxin abolished the acid secretory response induced by a bolus injection of pentagastrin in the continuously perfused stomach of the anaesthetized rat. Likewise, acid secretion stimulated by the continuous intravenous perfusion of pentagastrin was inhibited by administration of interleukin-1 beta (IL-1 beta). In both cases pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) but not dexamethasone or indomethacin substantially restored the secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration of L-arginine but not by its enantiomer D-arginine. Even though L-NAME increased blood pressure, this does no…
Nitric oxide mediates the inhibition by interleukin-1β of pentagastrin-stimulated rat gastric acid secretion
Bolus injection of interleukin-1 beta (2 micrograms kg-1, i.v.) inhibited acid secretion induced by intravenous infusion of pentagastrin (8 micrograms kg-1 h-1) in the continuously perfused stomach of the anaesthetized rat. Administration of interleukin-1 beta did not modify mean systemic arterial blood pressure. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 2-10 mg kg-1, i.v.), but not dexamethasone (5 mg kg-1, s.c. twice over 16 h), restored the acid secretory responses to pentagastrin. The actions of L-NAME were reversed by the prior administration of L-arginine (100 mg kg-1, i.v.), but not by its enantiomer D-arginine (100 mg kg-1, i.v.). L-NAME (5 mg kg-1, i.v.) increased…