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
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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