AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-08

AUTHORS

Bernardo Rodríguez-Iturbe, Tadashi Sato, Yasmir Quiroz, Nosratola D Vaziri

ABSTRACT

BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed. METHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months. RESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade. CONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis. More... »

PAGES

668-675

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1111/j.1523-1755.2004.00789.x

DOI

http://dx.doi.org/10.1111/j.1523-1755.2004.00789.x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1013159447

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15253721


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    "description": "BACKGROUND: The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed.\nMETHODS: The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months.\nRESULTS: As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade.\nCONCLUSION: The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.", 
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