Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9251
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dc.contributor.authorFabiani, Mark Een
dc.contributor.authorDinh, Diem Ten
dc.contributor.authorNassis, Len
dc.contributor.authorCasley, David Jen
dc.contributor.authorJohnston, Colin Ien
dc.date.accessioned2015-05-15T22:16:19Z
dc.date.available2015-05-15T22:16:19Z
dc.date.issued2000-09-01en
dc.identifier.citationAmerican Journal of Hypertension; 13(9): 1005-13en
dc.identifier.govdoc10981551en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9251en
dc.description.abstractThe present study examined the in vivo effects of candesartan cilexetil compared with losartan on angiotensin II (Ang II) receptor binding in the rat kidney after oral administration. Male Sprague-Dawley rats (250 to 300 g) were gavaged with candesartan cilexetil or losartan in doses of 0.1, 0.3, 1, 3, 10, or 30 mg/kg, or corresponding vehicle. Rats were killed at 0, 1, 2, 8, or 24 h after drug administration, trunk blood collected, and kidneys removed. The effects of candesartan cilexetil and losartan on Ang II receptor binding were determined by quantitative in vitro autoradiography using the radioligand [125I]-[Sar1,Ile8] Ang II. Ang II receptor binding in the kidney was mainly due to AT1 receptors with high levels of binding localized to the inner stripe of the outer medulla and glomeruli in cortical regions. Candesartan cilexetil (0.1 to 30 mg/kg) inhibited Ang II receptor binding to all anatomical sites of the kidney, in a dose-dependent manner. Losartan (0.1 to 30 mg/kg) also produced dose-dependent inhibition of Ang II receptor binding but was approximately 10- to 30-fold less potent than candesartan cilexetil. Inhibition of Ang II receptor binding was near maximal about 1 h after administration of candesartan cilexetil (10 mg/kg) or losartan (10 mg/kg), with both drugs producing persistent blockade at 24 h despite plasma renin activity and plasma drug concentrations returning to near normal levels. In vitro, candesartan, losartan, and EXP3174 (1 x 10(-10) to 1 x 10(-5) mol/L) displaced [125I]-[Sar1,Ile8] Ang II binding from AT1 receptors in the kidney in a concentration-dependent manner with a rank order of potency of candesartan > EXP3174 > losartan. The concentration required to displace 50% of radioligand binding (IC50) by candesartan, EXP3174, and losartan was 0.9+/-0.1 nmol/L, 3.4+/-0.4 nmol/L, and 8.9+/-1.1 nmol/L, respectively. In conclusion, the findings of the present study suggest that candesartan cilexetil is more potent than losartan in antagonizing AT1 receptors in the kidney in vivo. Nonetheless, both candesartan cilexetil and losartan produce rapid, complete, and sustained blockade of AT1 receptors in the rat kidney. Tissue blockade of Ang II receptors in target organs, such as the kidney, may contribute to the beneficial effects of Ang II receptor antagonists as antihypertensive agents.en
dc.language.isoenen
dc.subject.otherAngiotensin Receptor Antagonistsen
dc.subject.otherAnimalsen
dc.subject.otherBenzimidazoles.blood.pharmacologyen
dc.subject.otherBiphenyl Compounds.blood.pharmacologyen
dc.subject.otherImidazoles.metabolismen
dc.subject.otherKidney.metabolismen
dc.subject.otherLosartan.blood.pharmacologyen
dc.subject.otherMaleen
dc.subject.otherMembranes.metabolismen
dc.subject.otherOsmolar Concentrationen
dc.subject.otherRatsen
dc.subject.otherRats, Sprague-Dawleyen
dc.subject.otherReceptor, Angiotensin, Type 1en
dc.subject.otherReceptor, Angiotensin, Type 2en
dc.subject.otherReceptors, Angiotensin.metabolismen
dc.subject.otherRenin.blooden
dc.subject.otherTetrazoles.metabolismen
dc.titleIn vivo inhibition of angiotensin receptors in the rat kidney by candesartan cilexetil: a comparison with losartan.en
dc.typeJournal Articleen
dc.identifier.journaltitleAmerican Journal of Hypertensionen
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, VIC, Australiaen
dc.description.pages1005-13en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/10981551en
dc.type.austinJournal Articleen
item.grantfulltextnone-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
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