Increase in gastric intramucosal hydrogen ion concentration following endotoxin challenge in the rat and the actions of nitric oxide synthase inhibitors.


:1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxin lipopolysaccharide (LPS) was developed in the rat. The role of nitric oxide (NO) in these events in this model was evaluated using the non-selective NO synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA). 2. The pHi and intramucosal [H+] were evaluated in omeprazole-pretreated rats (30 mg/kg, i.p.) using the Henderson equation after estimating the PCO2 and the bicarbonate concentration in gastric wall. To measure gastric wall PCO2, the oesophagus was intubated and the pylorus ligated. The PCO2 was measured by a blood gas analyser in 2 mL saline instilled for 30 min in the gastric lumen to equilibrate with the gastric wall. The pHi was measured under basal conditions and 3 and 5 h after LPS (3 mg/kg) administration. Separate groups received treatment with L-NMMA (25-50 mg/kg) or L-NAME concomitantly or 2.5 h after administration of LPS. 3. Intravenous administration of Escherichia coli LPS provoked a significant fall in gastric pHi from 7.37 to 7.18 (median values; n =10-19) determined after 5 h. In groups treated concurrently with LPS and L-NAME (5 mg/kg; n = 19), there was a similar increase in intramucosal [H+] as that induced by LPS alone (n = 15) in those animals that survived. In contrast, L-NAME (5 mg/kg; n = 12), given 2.5 h after LPS challenge, at a time at which inducible NOS is known to be significantly expressed, prevented the increase in intramucosal [H+] at 3 and 5 h after LPS challenge. Similarly, L-NMMA (25-50 mg/kg; n = 23), given 2.5 h after LPS challenge, dose-dependently inhibited the increase in intramucosal [H+] at 3 and 5 h. 4. In conclusion, these findings indicate that this rat model could be useful in exploring the pathophysiology of acute endotoxin shock. Delayed administration of L-NAME and L-NMMA abolished the increase in gastric intramucosal [H+], supporting the involvement of excess NO in the tissue dysfunction associated with endotoxin shock. This suggests the potential value of this small animal model in evaluating the therapeutic activity of novel agents for use in septic shock.


Lamarque D,Whittle BJ





Has Abstract


2001-03-01 00:00:00














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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Winterhager E,Reuss B,Hellmann P,Spray DC,Gruemmer R

    更新日期:1996-12-01 00:00:00

  • Characterisation of a rat model of mechanical low back pain at an advanced stage using immunohistochemical methods.

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    journal_title:Clinical and experimental pharmacology & physiology

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    authors: Park TSW,Khan N,Kuo A,Nicholson JR,Corradini L,Smith MT

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  • Chronic exercise partially restores the transmural heterogeneity of action potential duration in left ventricular myocytes of spontaneous hypertensive rats.

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  • Dual nitric oxide mechanisms of cholestasis-induced bradycardia in the rat.

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    更新日期:2007-07-01 00:00:00

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    authors: Ikeda K,Nara Y,Nabica T,Fujimoto A,Endo J,Ishino H,Yamori Y

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  • Heat-killed Salmonella typhimurium mitigated radiation-induced lung injury.

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    authors: Head GA

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  • Lack of effect of bromocriptine on serum levels of calcium in the rat.

    abstract::1. The effect of bromocriptine (a prolactin suppressant drug) on the serum levels of calcium was studied in the male rat. The drug was administered subcutaneously at a dosage of 100 microgram per 100 g body weight three times per day. 2. Chronic treatment with bromocriptine had no significant effect on the serum calci...

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    authors: Tan CM,Tan GJ

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  • Defective intracellular Ca2+ homeostasis contributes to myocyte dysfunction during ventricular remodelling induced by chronic volume overload in rats.

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  • Effect of placental growth factor in models of experimental pre-eclampsia and trophoblast invasion.

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    authors: Yamagata K,Nara Y,Tagami M,Yamori Y

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  • Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aβ1-42 CA1-injected rats.

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    authors: Zamani E,Parviz M,Roghani M,Mohseni-Moghaddam P

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    abstract::1. Electrolytic lesions were made in various brain regions of the rat, and the effects of these lesions on nociceptive threshold and the antinociceptive actions of morphine were tested using a shock titration technique. 2. Lesions in the medial thalamus, the periaqueductal grey area, or the caudate nucleus, had no eff...

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    authors: Yeung JC,Yaksh TL,Rudy TA

    更新日期:1975-05-01 00:00:00

  • Piretanide and urinary excretion of ions in rat. Effect of indomethacin.

    abstract::1. Piretanide is a new loop diuretic resembling furosemide. The effects of this diuretic on various parameters of renal function and on the excretion of the major ions were studied on anaesthetized, hydrated rats. 2. Piretanide induced a marked diuresis and increased sodium, potassium, chloride and calcium excretion. ...

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    authors: Nguyen-Simonnet H,Gauthier C,Pellet M

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  • Systemic and regional haemodynamic responses to isoprenaline in conscious renal hypertensive rabbits.

    abstract::1. Using the electromagnetic flow probe and the radioactive microsphere technique, systemic and regional haemodynamic variables were measured in conscious normotensive and hypertensive rabbits. The rabbits were made hypertensive by unilateral nephrectomy combined with cellophane-wrapping of the remaining kidney and sy...

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    authors: van Boom M,Saxena PR

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    abstract::1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were a...

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    authors: Leung E,Mitchelson F

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  • The inhibitory response of the rabbit anococcygeus muscle.

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    authors: Wai SS,Coupar IM

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  • Effect of cold on fetal heart rate and its variability.

    abstract::1. The effects of cold saline (25 mL) injected over the fetal skin on fetal heart rate (HR) and HR variability (HRV), measured as the coefficient of variation (CV) in pulse interval (PI) and by power spectral analysis (PSA), were measured in 10 chronically catheterized fetal sheep aged 140-144 days. To determine the e...

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    authors: Yu ZY,Lumbers ER

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  • Hypertension through adrenaline activation of prejunctional beta-adrenoceptors.

    abstract::1. Adrenaline can enhance the stimulation-induced release of transmitter noradrenaline in sympathetically innervated tissues by activating prejunctional beta-adrenoceptors. 2. Adrenaline incorporated into sympathetic transmitter stores by neuronal uptake can be subsequently released as a co-transmitter and can then ac...

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    authors: Majewski H,Tung LH,Rand MJ

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    abstract::1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardi...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Dammanahalli KJ,Sun Z

    更新日期:2008-01-01 00:00:00

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    abstract::1. In coronary artery disease, the typical atheromatous plaque consists of a lipid core containing various inflammatory cells and a fibrous cap composed mostly of extracellular matrix. Both matrix metalloproteinases (MMPs) and inflammation are involved in the initiation of atherosclerotic plaques and plaque instabilit...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Zhang W,Wang CH,Li F,Zhu WZ

    更新日期:2008-03-01 00:00:00