Abstract:
:1. Endothelium-derived nitric oxide (NO), a major modulator of vascular tone, is synthesized from the terminal guanidino nitrogen of L-arginine. This reaction is inhibited by analogues of L-arginine, such as N-nitro-L-arginine methyl ester (L-NAME). Many of the biological effects of NO are mediated by the second messenger cGMP. NO is rapidly oxidized to NO3-, which, like cGMP, is eliminated via excretion into the urine. In a placebo controlled study, we investigated whether oral bolus administration of L-arginine and L-NAME affects the urinary excretion rates of NO3- and cGMP in Munich Wistar Frommter (MWF) rats. 2. Twenty MWF rats were kept in metabolic cages and received L-arginine (3 g/kg bodyweight), L-NAME (50 mg/kg), or placebo (0.9% saline) in randomized order. Urine samples were sequentially collected for 10 h and analysed for creatinine, NO3- and cGMP. 3. L-Arginine inducted a slight, but prolonged increase in urine flow, whereas L-NAME induced an early, transient increase in urine flow which was followed by a decrease. Creatinine clearance decreased by 65% after L-NAME, but was not affected by L-arginine or placebo. 4. Urinary NO3- and cGMP excretion rates transiently increased after L-arginine (NO3-: + 29%; cGMP: +16%) for 4-5 h, whereas L-NAME induced an immediate, pronounced and lasting inhibition of urinary NO3- and cGMP excretion (NO3-: -76%; cGMP: -46%). Urinary NO3- and cGMP excretions were significantly correlated (r = 0.755; P < 0.001). 5. Urinary excretion rates of NO3- and cGMP, expressed as mu mol/h, were correlated to urine flow (mL/h; r = 0.617 and 0.649, respectively; both P < 0.05), whereas after correction by urinary creatinine (mu mol/mmol creatinine) no correlation with urine flow was observed, indicating that these excretion rates were independent of renal excretory function. Thus we conclude that changes in the urinary excretion rates of NO3- and cGMP represent changes in NO production rates in vivo when expressed in relation to urinary creatinine. Urinary NO3- and cGMP excretion is modulated by acute NO synthase inhibition or substrate provision.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Boger RH,Bode-Boger SM,Gerecke U,Gutzki FM,Tsikas D,Frolich JCsubject
Has Abstractpub_date
1996-01-01 00:00:00pages
11-5issue
1eissn
0305-1870issn
1440-1681journal_volume
23pub_type
杂志文章abstract::1. Oxidative stress is believed to be an important mediator of neuronal cell death but the precise mechanism by which this occurs is unknown. 2. We have developed an in vitro model of neuronal oxidative stress to study the pathways by which free radicals kill neurones. 3. We have shown that oxidative stress, cystine d...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb02006.x
更新日期:1995-04-01 00:00:00
abstract::1. Pharmacological compounds that release nitric oxide (NO) have been useful tools in the evaluation of the broad role of NO in physiopathology and therapeutics. The present study compared the pharmacokinetics and pharmacodynamics of enalapril and an NO-releasing enalapril molecule (NCX899) in conscious male beagles. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04559.x
更新日期:2007-04-01 00:00:00
abstract::1. Atherosclerosis begins with the deposition of cholesterol in arterial tissue that is thought to be derived from circulating lipoproteins. There is considerable evidence implicating low density lipoprotein (LDL) as a primary source of plaque cholesterol and, consequently, there are many articles that deal with vario...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1997.tb01822.x
更新日期:1997-03-01 00:00:00
abstract::Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus (NDV) represents an attractive ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2011.05662.x
更新日期:2012-08-01 00:00:00
abstract::1. Intravenous endothelin-1 releases endothelium-derived relaxing factor (EDRF) and prostacyclin from the lungs, and substantial pulmonary clearance is claimed. Since these vaso-active substances could alter the haemodynamic effects of endothelin-1, the effects of boluses of endothelin-1 injected intravenously and int...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02521.x
更新日期:1994-04-01 00:00:00
abstract::Excessive activation of the sympatho-adrenomedullary system plays a pathogenic role in triggering and sustaining essential hypertension. We previously reported that, in normotensive rats, intracerebroventricularly (i.c.v.) administered neuropeptides, corticotropin-releasing factor and bombesin induced activation of th...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13297
更新日期:2020-07-01 00:00:00
abstract::1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure of 5/6 nephrectomized spontaneously hypertensive rats with salt loading was examined. 2. All nephrectomized rats were randomly assigned to one of four groups and their diet was cha...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03021.x
更新日期:1999-03-01 00:00:00
abstract::1. The concentration of methylguanidine and guanidinosuccinic acid has been measured in normal human plasma and discrepancies between various published methods for measuring methylguanidine have been resolved. Previous methods have been modified to allow these guanidines, together with guanidinoacetic acid and creatin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1978.tb00654.x
更新日期:1978-01-01 00:00:00
abstract::1. The differential identification of the angiotensin AT1A and AT1B receptor subtypes is impaired by the existing>96% homology of both receptors. In the present study, we characterized two polyclonal rabbit peptide antibodies, namely alpha-AT1A and alpha-AT1B, that recognize the C-terminal region of mouse AT1A and AT1...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2005.04288.x
更新日期:2005-11-01 00:00:00
abstract::1. Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K(+) current. DPI 201-106 is an experimental drug that produces QT prolongation by reducing Na(+) channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04805.x
更新日期:2007-12-01 00:00:00
abstract::1. The effects of bromocriptine and indomethacin on prolactin-induced pseudopregnancy were studied in pituitary grafted rats. 2.Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudopregnancy, effectively terminated it within 3...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00079.x
更新日期:1980-05-01 00:00:00
abstract::1. The aim of the present study was to produce a mathematical model that describes the way dynamic changes in renal sympathetic nerve activity affect renal, cortical and medullary blood flow. 2. Cortical blood flow (CBF) and medullary blood flow (MBF) were measured using laser-Doppler flowmetry and (total) renal blood...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03298.x
更新日期:2000-08-01 00:00:00
abstract::1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03552.x
更新日期:2001-11-01 00:00:00
abstract::1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovas...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1996.tb02750.x
更新日期:1996-05-01 00:00:00
abstract::1. A rapid imaging technique with temporal resolution of about 1 ms was employed to describe cell-length changes during the isotonic contraction cycle of adult rat ventricular myocytes at 22 degrees C. 2. Parameters of cell contraction and relaxation were defined and values obtained under control conditions and after ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01542.x
更新日期:1989-03-01 00:00:00
abstract::1. To investigate the effect of an exercise training programme on antihypertensive drug requirements, 19 sedentary subjects (14 men and five women) with mild essential hypertension (systolic blood pressure greater than 140 mmHg but less than 180 mmHg), aged 29-55 years, were randomly assigned to 16 weeks of moderate i...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1440-1681.1991.tb01445.x
更新日期:1991-05-01 00:00:00
abstract::This study aimed to evaluate the changes in left and right ventricular functions of children with obstructive sleep apnoea-hypopnoea syndrome (OSAHS) and to determine the efficacy of surgical treatment for OSAHS in children. The subjects included 20 normal controls and 55 children of OSAHS with adenoid and/or tonsil h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12408
更新日期:2015-06-01 00:00:00
abstract::Microglia are the resident immune cells within the brain and retina, commonly known as the macrophages of the central nervous system (CNS). Microglia survey the surrounding milieu to eliminate invading microbes, clear cellular debris and enforce programmed cell death by removing apoptotic cells. Complementary to their...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12099
更新日期:2013-08-01 00:00:00
abstract::1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation. 2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier-mediated efflux. 3. Release is also e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01375.x
更新日期:1991-01-01 00:00:00
abstract::Aerobic glycolysis plays a crucial role in cancer progression. Ketamine is often used for cancer pain relief in clinical settings. Moreover, ketamine inhibits proliferation and induces apoptosis in many cancer cell types. However, the anti-tumour mechanism of ketamine is still poorly understood. In the present study, ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13248
更新日期:2020-05-01 00:00:00
abstract::The effect of pancuronium in the rabbit ear artery was investigated in order to measure the inhibition it produces at the prejunctional muscarinic receptor on sympathetic nerve endings in this tissue. Pancuronium (0.1-0.2 mmol/l) produced an enhancement of responses to transmural electrical stimulation but this effect...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1983.tb00850.x
更新日期:1983-11-01 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. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper...
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. Structural changes in resistance vessels were studied sequentially (a) by hindquarter perfusion and (b) by planimetry of renal arterioles less than or equal to 20 micrometers radius, for 10 weeks during development of DOCA (deoxycorticosterone acetate)/salt hypertension in uninephrectomized rats and 5 weeks after c...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1982.tb00812.x
更新日期:1982-05-01 00:00:00
abstract::Contrast media are considered to cause acute kidney injury by activating various factors that induce renal vasoconstriction. We analysed the renal microvascular haemodynamic response using the Doppler flow wire method. Then changes in urinary liver-type fatty acid-binding protein levels following contrast medium admin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 信件
doi:10.1111/1440-1681.12653
更新日期:2016-11-01 00:00:00
abstract::1. Strips of rabbit anococcygeus muscle were submaximally contracted by the addition of phenylephrine to the bath fluid. 2. Acetylcholine, dimethylphenylpiperazinium and electrical field stimulation caused relaxation. Relaxation induced by acetylcholine and field stimulation was blocked by tetrodotoxin but only the ac...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1976.tb00598.x
更新日期:1976-03-01 00:00:00
abstract::Chemotherapy resistance is a major contributor to poor treatment responses and tumour relapse, the development of which has been strongly linked to the action of cancer stem cells (CSCs). Mounting evidence suggests that CSCs are reliant on low oxygen conditions and hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α)...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12693
更新日期:2017-02-01 00:00:00
abstract::1. The objectives of the study were to establish that inhibition of neuronal differentiation in culture (assessed by neurite outgrowth) can be used as a broad spectrum in vitro measure of neurotoxicity. 2. To establish whether a rapid measure of neurite outgrowth could be used. Thus the study examined the relationship...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1995.tb02017.x
更新日期:1995-05-01 00:00:00
abstract::1. In cats anaesthetized with alpha-chloralose, electrical stimulation (ES) of the trigeminal ganglion produced a fall in blood pressure, a predominantly ipsilateral dilatation in the common carotid vascular bed and bilateral dilatation of the middle meningeal vascular bed. Section of the trigeminal root abolished the...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1997.tb01206.x
更新日期:1997-06-01 00:00:00
abstract::1. The effects of ethacrynic acid were studied on relaxations elicited by nitric oxide (NO), the NO-donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN), nitrergic nerve stimulation and the NO-independent agent papaverine in isolated preparations of rat anococcygeus muscles. 2. Ethacrynic acid (100 mumol/L)...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02515.x
更新日期:1994-04-01 00:00:00