| Azelnidipine exerts renoprotective effects by improvement of renal microcirculation in angiotensin II infusion rats. | |
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MedLine Citation:
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PMID: 19666664 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Hypoxia-induced tubulointerstitial injury caused by loss of peritubular capillary (PTC) blood flow may be associated with progressive renal disease. Therefore, the maintenance of blood flow in PTCs may protect against loss of renal function. A long-acting calcium channel blocker, azelnidipine, has been shown to be useful in the treatment of progressive renal disease. However, its mechanism of action remains unclear. The aim of the present study was to elucidate whether azelnidipine maintains PTC blood flow and to compare it to nifedipine in its ability to improve tubulointerstitial injury caused by angiotensin II (AII) infusion in rats. METHODS: PTC blood flow was initially monitored using a pencil-lens interval microscope before and after intravenous AII (30 ng/kg/min) infusion with or without azelnidipine (10 microg/kg/min). Next, Wistar rats were treated with chronic infusion of AII (500 ng/kg/min) via an osmotic minipump with or without azelnidipine (3 mg/kg/day, orally) or nifedipine (60 mg/kg/day, orally) for 14 days, and tubulointerstitial damage (PTC loss, interstitial fibrosis, tubular atrophy) was examined. RESULTS: PTC blood flow was reduced after AII infusion but improved after a bolus injection of azelnidipine. Tubulointerstitial damage observed in chronically AII-treated kidneys was associated with hypoxic conditions, as indicated by the measurement of hypoxia biomarkers (intracellular hypoxyprobe-1 adducts). These tubulointerstitial injuries in AII-infused rats were more effectively reduced by azelnidipine than by nifedipine. The area showing hypoxic conditions in the kidney was also more reduced with azelnidipine than nifedipine treatment. CONCLUSIONS: Azelnidipine may increase PTC blood flow and improve renal hypoxia and tubulointerstitial injury induced by AII infusion. |
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Authors:
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Sohachi Fujimoto; Minoru Satoh; Hajime Nagasu; Hideyuki Horike; Tamaki Sasaki; Naoki Kashihara |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-07 |
Journal Detail:
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Title: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association Volume: 24 ISSN: 1460-2385 ISO Abbreviation: Nephrol. Dial. Transplant. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-25 Completed Date: 2010-02-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8706402 Medline TA: Nephrol Dial Transplant Country: England |
Other Details:
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Languages: eng Pagination: 3651-8 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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administration & dosage Animals Azetidinecarboxylic Acid / analogs & derivatives*, therapeutic use Calcium Channel Blockers / therapeutic use* Dihydropyridines / therapeutic use* Infusions, Intravenous Male Microcirculation / drug effects* Nephritis, Interstitial / physiopathology*, prevention & control* Nifedipine / therapeutic use* Rats Rats, Wistar Renal Circulation / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Dihydropyridines; 11128-99-7/Angiotensin II; 123524-52-7/azelnidipine; 21829-25-4/Nifedipine; 2517-04-6/Azetidinecarboxylic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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