Renal endothelial function and blood flow predict the individual susceptibility to adriamycin-induced renal damage
| Autor: | Richard P. E. van Dokkum, Peter Ochodnicky, Alex C. A. Kluppel, Hendrik Buikema, Robert H. Henning, Dick de Zeeuw, Marjolein van Wattum |
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| Přispěvatelé: | Groningen University Institute for Drug Exploration (GUIDE), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Groningen Institute for Organ Transplantation (GIOT), Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Nitroprusside medicine.medical_specialty DOXORUBICIN adriamycin nephrosis NEPHROPATHY medicine.medical_treatment Renal function PROGRESSION Kidney urologic and male genital diseases DISEASE Renal Circulation Nephropathy Nephrotoxicity RATS GLOMERULOSCLEROSIS endothelial function nitric oxide Internal medicine medicine Animals Rats Wistar NITRIC-OXIDE SYNTHASE Transplantation omega-N-Methylarginine business.industry renal blood flow Effective renal plasma flow medicine.disease Acetylcholine DYSFUNCTION Renal Plasma Flow Effective MODEL NG-Nitroarginine Methyl Ester medicine.anatomical_structure Endocrinology HEMODYNAMICS Nephrology Renal blood flow Disease Susceptibility Endothelium Vascular Hemodialysis business predictive value proteinuria Kidney disease |
| Zdroj: | Nephrology Dialysis Transplantation, 24(2), 413-420. Oxford University Press Nephrology, dialysis, transplantation, 24(2), 413-420. Oxford University Press |
| ISSN: | 0931-0509 |
| Popis: | Background. Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal perfusion in vivo predict the severity of renal damage in a model of adriamycin-induced nephropathy.Methods. In three separate studies, the following baseline parameters were measured in healthy male Wistar rats: (1) acetylcholine (ACh)-induced relaxation in small renal arteries in vitro (n = 16) and the contribution of prostaglandins, nitric oxide (NO) and endothelium-dependent hyperpolarizing factor (EDHF) to the relaxation; (2) glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in spontaneously voiding rats in vivo (n = 16) and (3) the acute effect of the NO-synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, n = 12) on renal blood flow (RBF) as compared to vehicle infusion (n = 9). Following these measurements, adriamycin (1.75 mg/kg i.v.) was injected and subsequent renal damage after 6 weeks was related to the baseline parameters.Results. Total ACh-induced (r = 0.51, P Conclusions. Individual animals with pronounced baseline endothelial dilatory ability measured in vitro and high ERPF in vivo are vulnerable to renal damage after the adriamycin injection. Acute inhibition of NO during adriamycin administration, resulting in a decrease of RBF, protects against renal injury, probably by limiting the delivery of the drug to the kidney. Therefore, interindividual variability in renal haemodynamics might be crucially involved in susceptibility to nephrotoxic renal damage. |
| Databáze: | OpenAIRE |
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