Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/13198
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dc.contributor.authorZhuo, Jen
dc.contributor.authorSong, Ken
dc.contributor.authorAbdelrahman, A Men
dc.contributor.authorMendelsohn, Frederick AOen
dc.date.accessioned2015-05-16T02:59:33Z
dc.date.available2015-05-16T02:59:33Z
dc.date.issued1994-07-01en
dc.identifier.citationClinical and Experimental Pharmacology & Physiology; 21(7): 557-67en
dc.identifier.govdoc7982288en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/13198en
dc.description.abstract1. The in vivo inhibition of angiotensin II (AII) receptor binding in the rat brain, kidney and adrenal was investigated after intravenous administration of the AT1-selective AII receptor antagonist losartan. 2. Male Sprague-Dawley rats were administered intravenously either vehicle, or losartan at doses of 1, 3 or 10 mg/kg. Plasma samples were collected and tissues removed at 1, 2, 8 or 24 h after administration of the antagonist. The effects of losartan on AII receptor binding were assessed by quantitative in vitro autoradiography. 3. Losartan significantly increased plasma renin activity (PRA) by six-fold and nine-fold at doses of 1 and 10 mg/kg, respectively (P < 0.05). Plasma losartan concentrations rose from 0.83 micrograms/mL at 1 mg/kg to 46.5 micrograms/mL at 10 mg/kg 1 h after administration of the drug. Plasma renin activity returned to control, whilst losartan was undetectable 24 h after injection of the antagonist. 4. In the brain, losartan produced a dose-dependent inhibition of AII receptor binding to the brain structures which express exclusively, or predominantly, AT1 receptors both outside and within the blood brain barrier. By contrast, losartan did not affect binding to the nuclei which contain exclusively, or predominantly, AT2 receptors. 5. In the kidney, losartan blocked AII receptor binding to all anatomical sites in a dose-dependent manner. The inhibition peaked at 1 h and persisted beyond 24 h despite the fact that PRA had returned to control, and losartan was not detectable in the circulation. In the adrenal gland, where AT1 and AT2 receptors occur in both the cortex and medulla, losartan caused partial inhibition at both regions. 6. These results indicate that losartan, administered intravenously at these doses, and/or its active metabolites, partially penetrate the blood brain barrier to selectively inhibit central AT1 receptors, and exert selective and prolonged blockade at AT1 receptors in peripheral target tissues.en
dc.language.isoenen
dc.subject.otherAdrenal Glands.drug effects.metabolismen
dc.subject.otherAngiotensin II.metabolismen
dc.subject.otherAngiotensin Receptor Antagonistsen
dc.subject.otherAnimalsen
dc.subject.otherAutoradiographyen
dc.subject.otherBiphenyl Compounds.blood.pharmacologyen
dc.subject.otherBlood-Brain Barrier.drug effectsen
dc.subject.otherBrain Chemistry.drug effectsen
dc.subject.otherDose-Response Relationship, Drugen
dc.subject.otherImidazoles.blood.pharmacologyen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherInjections, Intravenousen
dc.subject.otherKidney.drug effects.metabolismen
dc.subject.otherLosartanen
dc.subject.otherMaleen
dc.subject.otherRatsen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherRenin.blooden
dc.subject.otherTetrazoles.blood.pharmacologyen
dc.titleBlockade by intravenous losartan of AT1 angiotensin II receptors in rat brain, kidney and adrenals demonstrated by in vitro autoradiography.en
dc.typeJournal Articleen
dc.identifier.journaltitleClinical and Experimental Pharmacology & Physiologyen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.description.pages557-67en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/7982288en
dc.type.austinJournal Articleen
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
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