Nitric oxide induced sinusoidal relaxation after a propranolol priming dose in the perfused rat liver reduces propranolol availability on subsequent dosing.


:1. The present study sought to explain the mechanism leading to reduced availability of propranolol when given after a priming dose in the single-pass perfused rat liver. 2. Extracellular sucrose space (as a measure of sinusoidal relaxation) in perfused rat liver before and after propranolol or propranolol and N(G)-nitro-L-arginine methyl ester (L-NAME; nitric oxide (NO) synthase inhibitor) treatment were examined. The results showed that propranolol induces sinusoidal relaxation in the perfused liver and this effect could be abolished by NO synthase inhibitor L-NAME. 3. Two bolus injections of propranolol were given to the isolated perfused rat liver and outflow concentration-time profiles of intact propranolol were determined. A two-phase physiologically based organ pharmacokinetic model was applied to estimate hepatocellular influx, efflux, binding, ion-trapping and metabolic elimination pharmacokinetic parameters for propranolol. The recovery of propranolol in the second injection was approximately 54% of that in the first injection. The permeability-surface area product, the binding and the intrinsic clearance all increased significantly after prior exposure of the rat liver to the first bolus of propranolol (P < 0.05). 4. Based on the findings of the present study, we propose that the most likely explanation for the reduced availability of a second propranolol dose (after administration of a priming dose) in the perfused liver is a consequence of the NO-mediated sinusoidal relaxation effect of propranolol, arising from the priming dose. This observation supports the view that the pharmacokinetics of some drugs might be altered by the pharmacodynamic effects of the same drug given earlier in the perfused liver.


Liu X,Zou Y,Khlentzos AM,Yang Y,Nikolovski J,Weiss M,Roberts MS




Has Abstract


2010-10-01 00:00:00














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    abstract::1. Chronic alcohol treatment has been reported to be associated with liver and kidney damage. The insulin-like growth factor (IGF) is the major growth factor related to alcohol consumption. However, the effect of alcohol on the IGF system in the liver and kidney has not been fully elucidated. Thus, the present study w...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Park SH,Heo JS,Kang CW

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  • Interaction between epidermal growth factor and arginine vasopressin in renal medullary membranes.

    abstract::1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subt...

    journal_title:Clinical and experimental pharmacology & physiology

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    authors: Grant SL,Phillips PA,Gow CB

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  • Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus.

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    pub_type: 杂志文章


    authors: Bouhlel A,Bejaoui M,Ben Mosbah I,Hadj Abdallah N,Ribault C,Viel R,Hentati H,Corlu A,Ben Abdennebi H

    更新日期:2018-05-07 00:00:00

  • Toxic marine dinoflagellates in Singapore waters that cause seafood poisonings.

    abstract::1. The present paper reviews the toxic dinoflagellates found in Singapore waters that produce toxins that can accumulate through marine food chains to cause seafood poisonings. 2. Singapore waters contain dinoflagellate species linked to three types of seafood poisoning: paralytic shellfish poisoning, diarrhetic shell...

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  • Kynurenic acid, an endogenous glutamate antagonist, in SHR and WKY rats: possible role in central blood pressure regulation.

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    journal_title:Clinical and experimental pharmacology & physiology

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    authors: Kapoor V,Kapoor R,Chalmers J

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  • Urinary excretion of glycosaminoglycans, hydroxyproline and hydroxylysine in rabbits after excessive ingestion of fluoride.

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    journal_title:Clinical and experimental pharmacology & physiology

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    authors: Jha M,Koacher J,Susheela AK

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    authors: Imanishi T,Hano T,Takarada S,Nishio I

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    authors: Buchwald H,O'Dea TJ,Menchaca HJ,Michalek VN,Rohde TD

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    authors: Patzak A,Lai E,Persson PB,Persson AE

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    authors: Denoroy L,West MJ,Chalmers J

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    authors: Wang J,Cao DY,Guo Y,Ma SJ,Luo R,Pickar JG,Zhao Y

    更新日期:2011-08-01 00:00:00

  • Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy.

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    authors: Omodani H,Kinugawa T,Ogino K,Furuse Y,Yamaguchi M,Mori M,Endo A,Kato M,Kato T,Osaki S,Miyakoda H,Igawa O,Hisatome I,Shigemasa C

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  • Glycyrrhizin treatment ameliorates post-traumatic stress disorder-like behaviours and restores circadian oscillation of intracranial serotonin.

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    authors: Lai S,Shi L,Jiang Z,Lin Z

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    authors: Kanamori S,Sugiyama S,Goto H,Hayakawa T,Shimomura Y,Ozawa T

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    authors: Heller RF,Henry DA,Brent PJ

    更新日期:1989-10-01 00:00:00

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Kikuchi H,Shimada W,Nonaka T,Ueshima S,Tanaka S

    更新日期:1996-10-01 00:00:00

  • Integrative role of the lamina terminalis in the regulation of cardiovascular and body fluid homeostasis.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Johnson AK,Cunningham JT,Thunhorst RL

    更新日期:1996-02-01 00:00:00

  • Comparison of vaccination of mice and rats with Haemophilus influenzae and Bordetella pertussis as models of atopy.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Terpstra GK,Raaijmakers JA,Kreukniet J

    更新日期:1979-03-01 00:00:00

  • Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

    abstract::1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hy...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Bataillard A,Gomez-Sanchez CE,Vincent M,Touraine JL,Sassard J

    更新日期:1988-11-01 00:00:00

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Borg JJ,Hancox JC,Hogg DS,James AF,Kozlowski RZ

    更新日期:2004-01-01 00:00:00

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Laufer E,Reid C,Qi XL,Jennings GL

    更新日期:1998-03-01 00:00:00

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Burrell LM,Phillips PA,Stephenson J,Risvanis J,Hutchins AM,Johnston CI

    更新日期:1993-05-01 00:00:00

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Büsst CJ

    更新日期:2013-08-01 00:00:00

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    abstract::1. Studies of evolutionary temperature adaptation of muscle and locomotor performance in fish are reviewed with a focus on the Antarctic fauna living at subzero temperatures. 2. Only limited data are available to compare the sustained and burst swimming kinematics and performance of Antarctic, temperate and tropical s...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Franklin CE

    更新日期:1998-09-01 00:00:00

  • Identification of a pyridine derivative inducing senescence in ovarian cancer cell lines via P21 activation.

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    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Shang D,Wu Y,Ding Y,Lu Z,Shen Y,Zhu F,Liu H,Zhu C,Tu Z

    更新日期:2018-05-01 00:00:00