Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/13198
Title: Blockade by intravenous losartan of AT1 angiotensin II receptors in rat brain, kidney and adrenals demonstrated by in vitro autoradiography.
Authors: Zhuo, J;Song, K;Abdelrahman, A M;Mendelsohn, Frederick AO
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 1-Jul-1994
Citation: Clinical and Experimental Pharmacology & Physiology; 21(7): 557-67
Abstract: 1. 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.
Internal ID Number: 7982288
URI: http://ahro.austin.org.au/austinjspui/handle/1/13198
URL: http://www.ncbi.nlm.nih.gov/pubmed/7982288
Type: Journal Article
Subjects: Adrenal Glands.drug effects.metabolism
Angiotensin II.metabolism
Angiotensin Receptor Antagonists
Animals
Autoradiography
Biphenyl Compounds.blood.pharmacology
Blood-Brain Barrier.drug effects
Brain Chemistry.drug effects
Dose-Response Relationship, Drug
Imidazoles.blood.pharmacology
In Vitro Techniques
Injections, Intravenous
Kidney.drug effects.metabolism
Losartan
Male
Rats
Rats, Sprague-Dawley
Renin.blood
Tetrazoles.blood.pharmacology
Appears in Collections:Journal articles

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