Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12144
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dc.contributor.authorNayler, W Gen
dc.contributor.authorDillon, J Sen
dc.contributor.authorSturrock, W Jen
dc.contributor.authorBuckley, D Jen
dc.date.accessioned2015-05-16T01:47:40Z
dc.date.available2015-05-16T01:47:40Z
dc.date.issued1988-12-01en
dc.identifier.citationJournal of Cardiovascular Pharmacology; 12(6): 629-36en
dc.identifier.govdoc2467079en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12144en
dc.description.abstractExperiments were undertaken to establish whether the chronic administration of verapamil, to provide a therapeutically relevant plasma level, results in a loss of cardiac norepinephrine (NE) and, if so, whether this is accompanied by a change in cardiac beta 1-adrenoceptor density, affinity, or selectivity. Adult male Sprague-Dawley rats were used. Verapamil was mixed with the food to provide a daily verapamil intake of 50 mg/kg body weight. This yielded a plasma level of 80-110 ng/ml and caused a significant but reversible decrease in left ventricular NE (77%, p less than 0.001), dopamine (43%, p less than 0.02), and 3,4-dihydroxyphenylethyleneglycol (30%, p less than 0.02). Cardiac membranes prepared from rats maintained on standard (control) diet contained a single population of high affinity beta 1-adrenoceptor binding sites, with an affinity (Kd) of 0.24 +/- 0.02 nM and a density (Bmax) of 35.5 +/- 19.5 fmol/mg protein. Including verapamil (dissolved in either ethanol or water) in the diet for less than or equal to 6 weeks had no effect on the Kd, Bmax, or selectivity of these sites. However, the ethanol containing, but not the ethanol-free, placebo diet caused a small (p less than 0.05) reduction in Bmax after 6 but not after 2 weeks treatment. These results show that the chronic oral administration of verapamil to provide a clinically relevant plasma level depletes the cardiac stores of NE by 77% without causing an increase in beta 1-adrenoceptor density during 6 weeks therapy.en
dc.language.isoenen
dc.subject.otherAnesthetics.pharmacologyen
dc.subject.otherAnimalsen
dc.subject.otherBody Weight.drug effectsen
dc.subject.otherDieten
dc.subject.otherDihydroalprenolol.diagnostic useen
dc.subject.otherHeart.drug effectsen
dc.subject.otherMaleen
dc.subject.otherMyocardium.metabolismen
dc.subject.otherNorepinephrine.metabolismen
dc.subject.otherOrgan Size.drug effectsen
dc.subject.otherRatsen
dc.subject.otherRats, Inbred Strainsen
dc.subject.otherReceptors, Adrenergic, beta.drug effectsen
dc.subject.otherTime Factorsen
dc.subject.otherVerapamil.blood.pharmacologyen
dc.titleEffect of chronic verapamil therapy on cardiac norepinephrine and beta-adrenoceptor density.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of Cardiovascular Pharmacologyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.description.pages629-36en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/2467079en
dc.type.austinJournal Articleen
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
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