Abstract:
:1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP-selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2. In pentobarbitone-anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME) in a dose-response protocol (0.2-20 mg kg-1; n = 6) and as a single bolus of 10 mg kg-1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3. L-NAME caused a dose-dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose-dependent fall in cardiac output. A single bolus of L-NAME (10 mg kg-1) produced these effects within 15 min. 4. Subsequent administration of nicardipine (0.05-0.2 mg kg-1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5-10 mg kg-1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1-5 mg kg-1) had no significant effect on any of these variables. 5. These results suggest that reduced cardiac output following inhibition of NO synthesis is an effect of increased afterload on the heart and is reversible by nicardipine and to a lesser extent by theophylline.These findings may have potential value for those using NO synthase inhibitors to treat patients with septic shock.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Herity NA,Allen JD,Silke B,Adgey AAdoi
10.1111/j.1476-5381.1994.tb13089.xsubject
Has Abstractpub_date
1994-06-01 00:00:00pages
423-8issue
2eissn
0007-1188issn
1476-5381journal_volume
112pub_type
杂志文章abstract::The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand propert...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13350
更新日期:2015-12-01 00:00:00
abstract::In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the levels of ACh in hippocampal dialysates. The nicotine-induced hippocampal ACh release w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702683
更新日期:1999-07-01 00:00:00
abstract::1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb10580.x
更新日期:1969-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A neg...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2012-05-01 00:00:00
abstract::At nanomolar concentrations, SR141716 and AM251 act as specific and selective antagonists of the cannabinoid CB1 receptor. In the micromolar range, these compounds were shown to inhibit basal G-protein activity, and this is often interpreted to implicate constitutive activity of the CB1 receptors in native tissue. We ...
journal_title:British journal of pharmacology
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更新日期:2003-12-01 00:00:00
abstract::1. Transcriptional control of the human beta(2) adrenergic receptor gene (ADRB2) predominantly resides within a 549 base pair region immediately 5' to the start of translation. Within this region, four naturally occurring polymorphisms, -468 C-->G, -367 T-->C, -47 T-->C, and -20 T-->C, have been identified. 2. To dete...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704935
更新日期:2002-12-01 00:00:00
abstract::1. We have investigated the mechanism of smooth muscle contraction evoked by activation of 5-HT1-like receptors in dog isolated saphenous vein. 2. In the presence of the 5-HT2 receptor antagonist, ritanserin (0.1 microM), concentration-effect curves (10 nM-300 microM) for 5-hydroxytryptamine (5-HT)-induced smooth musc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09026.x
更新日期:1992-03-01 00:00:00
abstract::The sequence similarity within the amino-terminal regions of parathyroid hormone (PTH) and PTH-related protein (PTHrP) allows the two to share actions at a common site, the PTH1 receptor. A number of biological activities have been ascribed to actions of other domains within PTHrP. PTHrP production by late stage breas...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14709
更新日期:2019-05-14 00:00:00
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更新日期:2000-10-01 00:00:00
abstract::Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation const...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707672
更新日期:2008-04-01 00:00:00
abstract::1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16710.x
更新日期:1996-03-01 00:00:00
abstract::1 Plasma noradrenaline concentrations were similar in rats following unilateral renal arterial constriction (two kidney Goldblatt model) and in sham-operated control rats. 2 The development of hypertension was not affected by pretreatment with intracisternal injections of 6-hydroxydopamine. 3 These data suggest that s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08406.x
更新日期:1977-10-01 00:00:00
abstract::1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704395
更新日期:2001-12-01 00:00:00
abstract::1 The responses of the smooth muscle of the capsule and blood vessels of the isolated, blood-perfused spleen of the dog to angiotensin, oxytocin and vasopressin have been investigated and compared to the actions of the catecholamines, adrenaline and noradrenaline.2 Increasing doses of each of the three polypeptides ca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb06930.x
更新日期:1975-06-01 00:00:00
abstract::1 Very highly purified (greater than 100,000 u/mg) slow reacting substance of anaphylaxis (SRS-A) has been prepared by reversed phase high pressure liquid chromatographic (HPLC) techniques. 2 High resolution liquid chromatography suggests that SRS-A may exist in at least three distinct forms which are possible tautome...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10696.x
更新日期:1980-01-01 00:00:00
abstract::1. The effects of low oxygen tension on tone and on the responsiveness to contractile and relaxant agents were examined on circumflex coronary artery rings isolated from sheep. 2. When artery rings (2-2.5 mm o.d.) were set at their optimal resting tension, introduction of hypoxia (0% O2) caused a sustained contraction...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11894.x
更新日期:1989-04-01 00:00:00
abstract:UNLABELLED:Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancre...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13226
更新日期:2016-04-01 00:00:00
abstract::1. Losigamone is a novel anticonvulsant the mechanism of action of which is not known. This study investigated the effect of losigamone on spontaneous, NMDA- and AMPA-induced depolarizations in the cortical wedge preparation of the DBA/2 mouse (which are susceptible to sound-induced seizures) and on endogenous amino a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701539
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Strontium ranelate, a drug approved and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium-sensing (CaS) receptor. However, it is not known whether bone-targeted CaS receptor positive allosteric modulators (PAMs; calcimimetics) rep...
journal_title:British journal of pharmacology
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doi:10.1111/bph.14344
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abstract::1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adreno...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08775.x
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:7-Ketocholesterol, an oxysterol present in atherosclerotic lesions, induces smooth muscle cell (SMC) death, thereby destabilizing plaques. Statins protect patients from myocardial infarction, though they induce SMC apoptosis. We investigated whether statins and 7-ketocholesterol exerted additive ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.181
更新日期:2008-07-01 00:00:00
abstract::The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose-dependently decrease the positive chronotropic and inotropic effects, and the seve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11195.x
更新日期:1987-03-01 00:00:00
abstract::Histamine has been one of the most studied substances in medicine, playing a major role in diverse (patho)physiological processes. It elicits its multifaceted modulatory functions by activating four types of GPCRs, designated as H1-4 . Despite the heterogeneity and the complexity of histamine receptor pharmacology, ma...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14524
更新日期:2020-02-01 00:00:00
abstract::1. Aggressive behaviour was elicited in rats that had been deprived of food for 20 h daily (starved), by chronic administration of Cannabis sativa extract or (-)-Delta(9)-trans-tetrahydrocannabinol.2. The influence of intraperitoneal (i.p.) or oral glucose administration, cold environment, acidosis, and corn, and prot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07317.x
更新日期:1972-04-01 00:00:00
abstract::1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosp...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12391.x
更新日期:1991-09-01 00:00:00
abstract::1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14127.x
更新日期:1990-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15064
更新日期:2020-08-01 00:00:00
abstract::1. The present study characterizes and classifies alpha 1-adrenoceptor-mediated vasoconstriction in the isolated perfused kidney of rat using quantitative receptor pharmacology and compares the results to radioligand binding studies (made in cloned alpha 1-adrenoceptor subtypes, native alpha 1A-adrenoceptors in submax...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15875.x
更新日期:1995-05-01 00:00:00
abstract::1. The aim of the present experiments was to determine whether 5-HT1A receptors play a role in the control of the reflex activation of pulmonary vagal motoneurones. This was carried out by investigating the effects of intracisternal injections (i.c.) of the 5-HT1A receptor ligands, 8-OH-DPAT (50 micrograms kg-1), busp...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15250.x
更新日期:1996-02-01 00:00:00
abstract::1. Some hydroxy-, amino-, and methoxy- phenylalkyltrimethylammonium compounds, beta-pyridylmethyl- dimethylamine and pyrrolidine, and beta-pyridylethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (-)-nicotine.2. The o- and m- hydroxybenzyl-, o-hydroxyphenet...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb10372.x
更新日期:1970-07-01 00:00:00