Abstract:
AIMS:Smoking is a major risk factor for developing atherosclerosis. In order to understand the vascular abnormalities observed in smokers, we investigated vascular responsiveness in cigarette smokers. METHODS:We performed two consecutive matched group comparative studies to investigate vascular responsiveness using venous occlusion plethysmography. The mean effects of three incremental doses of each vasoactive agent are presented. Both studies compared smokers with nonsmokers. RESULTS:The first investigated 68 subjects (smokers = 29; mean +/- s.d. ages; 24 +/- 6 vs 25 +/- 5 years; P = NS) and found smoking was associated with a significant blunting of the flow ratio between treated and untreated arms to endothelium-dependent vasodilatation to acetylcholine (mean +/- s.d., nonsmokers vs smokers) 4.07 +/- 2.18 vs 3.42 +/- 1.79 (P = 0.04, 95% CI 0.02, 1.12). By contrast, there was no significant difference in the responses to the endothelium-independent vasodilators sodium nitroprusside and verapamil. Smoking was also associated with a significant impairment in endothelium-dependent vasoconstriction induced by monomethyl-L-arginine (L-NMMA) 0.78 +/- 0.22 vs 0.87 +/- 0.21 (P = 0.006, 95% CI -0.14, -0.02) and a trend to blunted endothelium-independent vasoconstrictor responses to noradrenaline. In the second study we investigated the response to angiotensin I and II in 23 subjects (smokers = 12; mean +/- s.d. ages; 34 +/- 10 vs 32 +/- 11 years). There was significant impairment in smokers of the mean vasoconstrictor response to angiotensin I 0.51 +/- 0.15 vs 0.59 +/- 0.16 (nonsmokers vs smokers; P = 0.003, 95% CI -0.13, -0.03) and a nonsignificant trend towards impairment of the response to angiotensin II. CONCLUSIONS:Cigarette smoking in male volunteers is associated with blunted basal and stimulated nitric oxide bioactivity. Endothelial independent vasodilator responses (to nitroprusside and verapamil) were unaltered in smokers. A defect in the vasoconstrictor response to angiotensin I was also seen.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Butler R,Morris AD,Struthers ADdoi
10.1046/j.0306-5251.2001.01434.xkeywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
145-9issue
2eissn
0306-5251issn
1365-2125pii
bcp434journal_volume
52pub_type
临床试验,杂志文章abstract:AIMS:The aim of this study was to use data from an experimental induced blood stage malaria clinical trial to characterize the antimalarial activity of the new compound Actelion-451840 using pharmacokinetic/pharmacodynamic (PK/PD) modelling. Then, using simulations from the model, the dose and dosing regimen necessary ...
journal_title:British journal of clinical pharmacology
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abstract:AIMS:The protease inhibitor indinavir is characterized by an important interindividual pharmacokinetic variability, which results from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A and the multidrug efflux pump P-glycoprotein (P-gp), encoded by MDR1. Using a population pharmacokinetic approach, we in...
journal_title:British journal of clinical pharmacology
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abstract:AIMS:Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS:DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transport...
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doi:10.1111/bcp.13186
更新日期:2017-05-01 00:00:00
abstract:AIMS:Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). METHODS:We studied 264 IMA rings taken from 65 patients undergoing co...
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abstract:AIMS:The Transdermal Delivery System (TDS) is a liquid formulation that can be applied to the skin via a metered pump spray to deliver drug to the systemic circulation. The aims of this study were to assess the ability of the TDS preparation to deliver testosterone systemically, and to characterize the pharmacokinetic ...
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abstract::1. Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. We therefore studied the reproducibility of powe...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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abstract:AIMS:In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury wo...
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abstract:UNLABELLED:What is already known about this subject? The naturally occurring interlukin-1 receptor antagonist (IL-1RA) markedly protects rodents against ischaemic, excitotoxic and traumatic brain injury, suggesting it may be of therapeutic value. When administered intravenously to patients soon after stroke, IL-1RA is ...
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abstract::The effect of fatty degeneration of liver parenchyma on drug metabolism was investigated in 21 obese non-insulin-dependent diabetic subjects by measuring plasma antipyrine kinetics, hepatic cytochrome P-450, liver size and the extent of fatty infiltration. The hepatic drug metabolising capacity, as measured by total a...
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abstract::The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therap...
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:British journal of clinical pharmacology
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abstract::1. Endogenous dopamine, acting through specific receptors on blood vessels, renal tubules and adrenal cortical cells, may play a role in the development and maintenance of the hypertensive state. 2. In hypertensive patients, activation of the DA1-receptor with intravenous fenoldopam produces a rapid and sustained redu...
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abstract::1. An open-label, randomised study was performed to assess the effect of tenidap sodium on the pharmacodynamics and plasma protein binding of warfarin. 2. Fourteen healthy male volunteers received either a single oral dose of 120 mg tenidap sodium or matching placebo capsules from days 11 to 36. A single oral dose of ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:British journal of clinical pharmacology
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abstract::1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine wi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb05295.x
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abstract::1 The effect of pregnancy on the binding of phenytoin and phenobarbitone to serum proteins was studied in normal women and in drug treated epileptic women. 2 The binding of both drugs was reduced during pregnancy. The reduction correlated positively with the gestational age and negatively with the serum albumin concen...
journal_title:British journal of clinical pharmacology
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doi:10.1111/j.1365-2125.1982.tb01420.x
更新日期:1982-04-01 00:00:00
abstract::The effect of isotonic bicycle exercise on beta 2-adrenoceptors and cAMP production in lymphocytes was studied. The origin of the newly exposed receptors was studied by measuring radioligand binding in the presence of hydrophylic or lipophylic 'cold' ligands. During exercise beta 2-adrenoceptor density increased from ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb05487.x
更新日期:1990-01-01 00:00:00