Abstract:
: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.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Lamarque D,Whittle BJdoi
10.1046/j.1440-1681.2001.03432.xkeywords:
subject
Has Abstractpub_date
2001-03-01 00:00:00pages
164-8issue
3eissn
0305-1870issn
1440-1681pii
cep3432journal_volume
28pub_type
杂志文章abstract::1. Hypertension plays a critical role in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD), but it has also been postulated that antihypertensive drugs that block the renin-angiotensin system (RAS) show class-specific renoprotective actions beyond their blood pressure (BP)-lowering effe...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.05453.x
更新日期:2010-12-01 00:00:00
abstract::1. NBPA is a derivative of 3-n-butylpathalide isolated from Apium granolens Linn. 2. At concentrations ranging from 6 x 10(-6) to 10(-6) mol/L, NBPA inhibited the L-type calcium current in guinea-pig myocardial cells and cultured human neuroblastoma cells. 3. At 10(-6) mol/L, NBPA markedly inhibited calcium-dependent ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03144.x
更新日期:1999-10-01 00:00:00
abstract::1. One hour exposure to hyperoxia has been shown previously to limit a subsequent ischaemia-reperfusion injury in spontaneously breathing rats. We tested the cardioprotective effect of a shorter period of hyperoxia during mechanical ventilation and the possible contribution of reactive oxygen species (ROS) and mitocho...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04745.x
更新日期:2008-01-01 00:00:00
abstract::Afferent splanchnic nerve stimulation with different frequencies in Wistar Kyoto rats caused depressor and pressor responses depending on the frequency employed. Similar visceral afferent activation in spontaneously hypertensive rats caused depressor responses at all frequencies of stimulation. It is suggested that th...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1985.tb00300.x
更新日期:1985-01-01 00:00:00
abstract::1. Ischaemia-reperfusion (IR) injury is an important contributor to tissue damage and has been shown to be attenuated by preconditioning (PC) in some animal models. A recent report has suggested that the forearm can be used for the study of this phenomenon in humans. We aimed to reproduce and further characterize this...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1440-1681.2005.04163.x
更新日期:2005-01-01 00:00:00
abstract::1. Mathematical modelling is useful in pharmacology, allowing the investigator to obtain insights into the biological processes under study that may not always be intuitively obvious. Examples are presented in this review using the pharmacology of the muscarinic acetylcholine receptor (mAChR) agonist xanomeline. 2. Xa...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03376.x
更新日期:2001-03-01 00:00:00
abstract::Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohu...
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pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12694
更新日期:2017-02-01 00:00:00
abstract::Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different cla...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12335
更新日期:2015-02-01 00:00:00
abstract::KISS1 and KISS1R, a novel pair of metastasis suppressors, are likely to be associated with the prognosis of colorectal cancer (CRC). Here, a meta-analysis was performed to study the role of KISS1 and KISS1R in CRC. Heterogeneity, stability and publication bias were all estimated. Six publications describing a total of...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,meta分析
doi:10.1111/1440-1681.13093
更新日期:2019-07-01 00:00:00
abstract::1. The renal medulla plays an important role in regulating body sodium and fluid balance and blood pressure homeostasis through its unique structural relationships and interactions between renomedullary interstitial cells (RMIC), renal tubules and medullary vasculature. 2. Several endocrine and/or paracrine factors, i...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03277.x
更新日期:2000-07-01 00:00:00
abstract::1. Subpressor calcium infusion for 1 h, which raised calcium levels to the upper limit of normal in normal subjects, increased plasma and urinary levels of atrial natriuretic peptide (ANP). 2. Heart rate fell, presumably due to carotid baroreflex stimulation (supported by the fall in noradrenaline) and the resultant f...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00459.x
更新日期:1992-05-01 00:00:00
abstract::Mutations of αB-crystallin (CryαB), a small heat shock protein abundantly expressed in cardiac and skeletal muscles, are known to cause desmin-related myopathies. The CryαB R120G allele has been linked to a familial desminopathy and, in transgenic mice, causes a sudden death at about 28 weeks of age. To investigate th...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12253
更新日期:2014-08-01 00:00:00
abstract::1. Prenatal dexamethasone leads to low birth weight and compromises organogenesis, but its effects on nephrogenesis in male and female rats have not yet been investigated extensively. Reduced renal mass may be responsible for hypertension and renal haemodynamic and morphological adjustments to maintain the glomerular ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03787.x
更新日期:2003-01-01 00:00:00
abstract::1. Oxidative stress plays a role in senescence-associated organ deterioration. This is supported by the beneficial effects of anti-oxidants against ageing-related organ damage, although their role in cardiac ageing has not been elucidated. 2. The aim of the present study was to examine the impact of cardiac-specific o...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04540.x
更新日期:2007-01-01 00:00:00
abstract::1. Breast cancer resistance protein (BCRP, ABCG2) is a drug efflux transporter that is believed to affect the drug disposition of several drugs and xenobiotics. In the present study, we evaluated the localization and functional expression of BCRP in the human choriocarcinoma cell line BeWo, an in vitro model of the hu...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04324.x
更新日期:2006-01-01 00:00:00
abstract::Diabetes mellitus and depressive disorders are both common chronic diseases that increase functional disability and social burden. Cognitive impairment is a potentially debilitating feature of depression. Previous evidence indicates that the antidiabetic drug metformin could be suitable for diabetic patients with cogn...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,随机对照试验
doi:10.1111/1440-1681.12265
更新日期:2014-09-01 00:00:00
abstract::1. Adenosine A(1) receptors (A(1)R) play an important role in cardioprotection against hypoxic damage and the opening of mitochondrial permeability transition pores (MPTP) is central to the regulation of cell apoptosis and necrosis. However, it is still unclear whether A(1)R open MPTP in hypoxic cardiomyocytes. 2. The...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05300.x
更新日期:2010-03-01 00:00:00
abstract::1. Resistance changes of the afferent and efferent arterioles determine blood flow and filtration rate in the kidney. The tone of both vessels results from the influence of nerves and humoral and paracrine factors, through a balance of constrictor and dilator systems. Angiotensin (Ang) II and nitric oxide (NO) are imp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2005.04203.x
更新日期:2005-05-01 00:00:00
abstract::The inhibitory effect of morphine on intestine was observed by following the intestinal transit of a charcoal meal. This inhibitory effect of morphine was antagonized by naloxone. In addition, the inhibitory effect of morphine was also suppressed by prior administration of yohimbine and phentolamine. However, prazosin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00873.x
更新日期:1984-11-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
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更新日期:2008-08-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2000.03202.x
更新日期:2000-01-01 00:00:00
abstract::1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC) and (-)-epigallocatechin-3-gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique. 2. At co...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03796.x
更新日期:2003-01-01 00:00:00
abstract::Serotonin causes a dose related (0.1-20 micrograms/kg i.v.) increase in mean arterial blood pressure (MAP) and heart rate in conscious sheep. Ketanserin (0.1 mg/kg per h i.v.) causes a decrease in blood pressure, and an increase in heart rate. In the presence of ketanserin, serotonin induced increases in MAP are atten...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00872.x
更新日期:1984-11-01 00:00:00
abstract::1. Raised intracranial pressure (ICP) is a major factor associated with morbidity and mortality in patients with severe head injury. Identifying the mechanisms responsible for raised ICP may be difficult and, as a result, treatment prescribed may be non-specific and often ineffective. 2. Research aimed at obtaining mo...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1998.tb02350.x
更新日期:1998-11-01 00:00:00
abstract::This study evaluates the association between the long noncoding RNA GAS5 levels and the anti-proliferative effect of the glucocorticoid (GC) methylprednisolone (MP) alone and in combination with rapamycin in peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The effect of MP, rapamycin, and MP pl...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12572
更新日期:2016-06-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05085.x
更新日期:2009-04-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04699.x
更新日期:2007-11-01 00:00:00
abstract::1. The effect of pretreatment with nifedipine on naloxone-stimulated corticotrophin-releasing hormone (CRH)-induced adrenocorticotrophin (ACTH) release in humans was investigated. The mean peak plasma ACTH and cortisol levels and the mean peak change in cortisol levels from basal were significantly lower in the nifedi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01451.x
更新日期:1991-05-01 00:00:00
abstract::1. 125I-351A, a tyrosyl derivative of the angiotensin converting enzyme (ACE) inhibitor lisinopril, was used as a radioligand, and radioinhibitor binding and displacement assays have been established. 2. The in vitro potency of a range of ACE inhibitors against rat ACE was determined using the radioinhibitor binding d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1988.tb01053.x
更新日期:1988-02-01 00:00:00
abstract::1. None of the genes responsible for essential hypertension has been identified. Recent work in genetically hypertensive rats has shown linkage of blood pressure with alleles of the renin gene. Since the renin gene is a member of a conserved synteny group that in humans spans chromosome 1q21.3-32.3 and includes the ge...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01464.x
更新日期:1991-05-01 00:00:00