[{"key":"dc.contributor.author","value":"Lee, Andrew B. H.","language":null},{"key":"dc.date.accessioned","value":"2009-08-06T00:00:00","language":null},{"key":"dc.date.available","value":"2009-08-06T00:00:00","language":null},{"key":"dc.date.issued","value":"2001","language":null},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/11791","language":null},{"key":"dc.description.abstract","value":"In chronic renal failure (CRF), inability to concentrate urine is, in part, due to\r\ndownregulation of aquaporin 2 (AQP2) in the renal collecting duct. In the\r\npresent study; we investigated the interrelationship of endothelin (ET),\r\nvasopressin, and AQP2 in the inner medullary collecting duct (IMCD) of kidneys\r\nobtained from CRF (5\/6 nephrectomized) and control rats (sham-operated).\r\nTwo series of experiments were performed. In the first series, clearance\r\nstudies showed that serum BUN increased in the CRF rats by 53.2% (from\r\n23.27 \u00b1 1.08 to 49.75 \u00b1 3.13 mg%, p < 0.01). GFR decreased by 61.5% (from\r\n0.89 \u00b1 0.04 to 2.31 \u00b1 0.09 ml\/min, p < 0.01), and FEH2O increased by 81.0%\r\n(from 0.68 \u00b1 0.05 to 3.57 \u00b1 0.27 %, p < 0.01). ET-1 mRNA in the CRF rat IMCD\r\nincreased by 56.3% (from 0.31 \u00b1 0.04 to 0.71 \u00b10.10 amol\/\u03bcg, p < 0.01). ETB\r\nmRNA decreased by 55.7% (from 14.00 \u00b1 0.70 to 6.20 \u00b1 0.43 amol\/\u03bcg, p <\r\n0.01). AQP2 mRNA decreased by 31.9% (from 13.90 \u00b1 0.73 to 9.74 \u00b1 0.83\r\namol\/\u03bcg, p < 0.01). Changes of the ETB mRNA correlated with the changes in\r\nAQP2 mRNA, whereas changes in ET-1 mRNA inversely correlated with the\r\nchanges in AQP2 mRNA. In the second series of experiment, an ACE inhibitor,\r\nenalapril, was administered to control and CRF rats. Animals were divided to 2\r\nsubgroups: group 1 consisted of control and CRF rats without any treatment;\r\ngroup 2 comprised of control and CRF rats treated with enalapril. Renal\r\nclearance studies showed no significant renal functional improvement after\r\nenalapril treatment. In CRF treated rats, serum BUN increased by 55.6% and\r\nGFR decreased by 58.0% compared to the control treated rats. In group one\r\n(without treatment), ET-1 mRNA increased by 69.9% (from 0.31 \u00b1 0.03 to 1.03 \u00b1\r\n0. 26 amol\/\u03bcg, p < 0.01). ETB mRNA decreased by 65.8% (from 15.50 + 0.38 to\r\n5.30 \u00b1 0.36 amol\/\u03bcg, p < 0.01). V2R mRNA decreased by 50.9% (from 1350.13\r\n\u00b1 222.92 to 662.68 \u00b1 162.47 amol\/\u03bcg, p < 0.01). AQP2 mRNA decreased by\r\n29.7% (from 13.45 \u00b1 1.34 to 9.46 \u00b1 0.60 amol\/\u03bcg, p < 0.01) in the CRF rats. In\r\ngroup 2 (enalapril treated), ET-1 mRNA increased by 41.1% (from 0.33 \u00b1 0.07\r\nto 0.56 \u00b1 0.05 amol\/\u03bcg, p < 0.01). ETB decreased by 43.9% (from 16.18 \u00b1 1.09\r\nto 9.07 \u00b1 0.53 amol\/\u03bcg, p < 0.01). V2R decreased by 40.4% (from 1558.76 \u00b1\r\n129.64 to 929.40 \u00b1 211.83 amol\/\u03bcg, p < 0.01). AQP2 decreased by 12.5%\r\n(from 20.68 \u00b1 0.72 to 18.10 \u00b1 2.17 amol\/\u03bcg, p < 0.01) in the CRF rats. In situ\r\nhybridization images confirmed these results. Compared to the comparable\r\ncontrol rats, immunoblotting showed that V2R protein decreased by 52.4% and\r\n42.9% in the untreated CRF and treated CRF rats, and AQP2 protein level\r\ndecreased by 29.0% and 11.8% respectively. Although enalapril partially\r\nrestored V2R and AQP2 mRNA level in the CRF rats, there was no significant\r\nchange in the FEH2O after treatment. These data indicate that:\r\n1. ET-1 mRNA increased, whereas ETB, V2R, and AQP2 mRNA decreased in\r\nthe IMCD of CRF rats.\r\n2. ACE inhibitor enalapril partially normalized ET-1, ETB, V2R, and AQP2\r\nmRNA changes in the IMCD of the CRF rats.\r\n3. Enalapril partially restored V2R and AQP2 protein levels in the IMCD of CRF\r\nrats.\r\n4. Enalapril did not improve overall renal function in the CRF rats. 5. Enalapril partially corrected AQP2 mRNA levels, but failed to normalize\r\nFEH2O in the CRF rats, suggesting that collecting duct AQP2 level is partially\r\nresponsible for the urine concentrating defect in this renal segment.","language":"en"},{"key":"dc.format.extent","value":"8489917 bytes","language":null},{"key":"dc.format.mimetype","value":"application\/pdf","language":null},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":null},{"key":"dc.rights","value":"For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https:\/\/open.library.ubc.ca\/terms_of_use.","language":null},{"key":"dc.title","value":"Downregulation of vasopressin receptor and aquaporin 2 in the inner medullary collecting duct of chronic renal failure kidney : significance of angiotensin II and endothelin regulation","language":"en"},{"key":"dc.type","value":"Text","language":null},{"key":"dc.degree.name","value":"Master of Science - MSc","language":"en"},{"key":"dc.degree.discipline","value":"Experimental Medicine","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":null},{"key":"dc.date.graduation","value":"2001-11","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":null},{"key":"dc.description.affiliation","value":"Medicine, Department of","language":null},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]