ACE inhibition has adverse renal effects during dietary sodium restriction in proteinuric and healthy rats
Autor: | van Harry Goor, Inge Hamming, Menno J. A. Kocks, Gerarda Navis |
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Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP) |
Rok vydání: | 2006 |
Předmět: |
Male
Afferent arterioles Gene Expression BLOOD-PRESSURE Angiotensin-Converting Enzyme Inhibitors Kidney Renovascular hypertension low sodium GLOMERULAR-FILTRATION interstitial damage biology Reverse Transcriptase Polymerase Chain Reaction Arterioles Proteinuria medicine.anatomical_structure Nephrosis Kidney Diseases RENOVASCULAR HYPERTENSION medicine.medical_specialty food.diet Low sodium diet CONTROLLED-TRIAL MICE LACKING Pathology and Forensic Medicine afferent arterioles food Internal medicine Renin–angiotensin system medicine Animals cardiovascular diseases RNA Messenger Rats Wistar RECEPTOR business.industry ANGIOTENSIN-CONVERTING-ENZYME RENIN Kidney metabolism Angiotensin-converting enzyme Sodium Dietary ACE inhibition medicine.disease Rats Endocrinology Collagen Type III JUXTAGLOMERULAR CELLS Doxorubicin biology.protein business Heme Oxygenase-1 Low sodium |
Zdroj: | JOURNAL OF PATHOLOGY, 209(1), 129-139. Wiley |
ISSN: | 0022-3417 |
Popis: | Angiotensin-converting enzyme inhibitors (ACEi) provide renoprotection. A low sodium diet enhances their efficacy. However, the added effect of sodium restriction on proteinuria and blood pressure is not invariably associated with better preservation of renal morphology, suggesting that the combination of ACEi with a low sodium diet can elicit renal structural abnormalities. To test this hypothesis, the effects of ACEi in combination with a control (CS) or a low sodium (LS) diet were investigated in healthy rats and in adriamycin nephrotic rats. After 3 weeks of treatment, rats were sacrificed and kidneys examined for renal structural abnormalities. In healthy rats, ACEi reduced blood pressure: the fall in blood pressure was significantly greater in the ACEi/LS group. Renal morphology was normal in the ACEi/CS group but severe interstitial damage was found in the ACEi/LS group. This was associated with increased interstitial macrophage influx and up-regulation of osteopontin, alpha-smooth muscle actin, and collagen III expression. In addition, ACEi/LS induced an increase in the total medial area of afferent arterioles. In nephrotic rats, ACEVLS reduced both blood pressure and proteinuria, whereas only blood pressure was reduced in the ACEi/CS group. Mild interstitial damage was present in the ACEi/CS group but, strikingly, pronounced tubulo-interstitial abnormalities occurred in the ACEi/LS group, similar to those seen in ACEi/LS healthy rats, with similar changes in afferent arteriolar walls. In conclusion, the combination of ACEi/LS elicits pronounced renal interstitial abnormalities in healthy and nephrotic rats, despite a significant reduction of proteinuria in the latter. Considering their occurrence in healthy rats, these renal adverse effects cannot be due to specific characteristics of adriamycin nephrosis. Further studies should elucidate the mechanisms underlying these observations and their impact on long-term renoprotection. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
Databáze: | OpenAIRE |
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