Abstract | BACKGROUND:
Nephrosis-induced endothelial dysfunction is assumed to play a main role in cardiovascular morbidity. Adriamycin-induced proteinuria is a well-established rat model for nephrotic syndrome. However, induction of nephrosis by intravenous adriamycin administration might exert direct adriamycin cardiovasculotoxicity that could obscure or modify nephrosis-induced vascular dysfunction. The present study, therefore, investigated in vitro vascular function in the isolated thoracic aorta and isolated perfused hearts of rats with adriamycin nephrosis, as compared to non-nephrotic adriamycin exposed rats. METHODS: RESULTS: Exposure of the kidneys to adriamycin induced severe proteinuria with corresponding systemic nephrosis, as apparent from hypercholesterolaemia. Adriamycin exposure of the vascular bed led to marked blunting of the aortic response to the endothelium-dependent vasodilator, acetylcholine (ACh), both in non-nephrotic and nephrotic rats. The nephrotic state reduced the bradykinin-induced increase in coronary flow and enhanced the aortic constrictor response to angiotensin II associated with reduced basal aortic NO-activity, as shown by the comparison between adriamycin nephrotic rats and healthy and adriamycin controls. CONCLUSIONS:
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Authors | Nadir Ulu, Hendrik Buikema, Wiek H van Gilst, Gerjan Navis |
Journal | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
(Nephrol Dial Transplant)
Vol. 23
Issue 6
Pg. 1854-60
(Jun 2008)
ISSN: 1460-2385 [Electronic] England |
PMID | 18218687
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Animals
- Blood Pressure Determination
- Cardiovascular System
(drug effects, pathology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Doxorubicin
(adverse effects, pharmacology)
- Endothelium, Vascular
(drug effects)
- Male
- Nephrotic Syndrome
(chemically induced, pathology)
- Proteinuria
(chemically induced, physiopathology)
- Rats
- Rats, Wistar
- Reference Values
- Regional Blood Flow
(drug effects, physiology)
- Sensitivity and Specificity
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