| The Role of Blood Pressure and the Renin-Angiotensin System in Development of Diabetic Nephropathy (DN) in eNOS-/- db/db Mice. | |
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MedLine Citation:
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PMID: 22114203 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Randomized clinical trials have clearly shown that inhibition of the renin-angiotensin system (RAS) will slow the rate of progression of diabetic nephropathy, but controversy remains about whether the observed beneficial effects result from more than control of blood pressure. Deletion of eNOS in a model of type II diabetes, db/db mice (eNOS(-/-) db/db), induces an accelerated nephropathy and provides an excellent model of human diabetic nephropathy. As is frequently seen in type II diabetes, blood pressure is moderately elevated in eNOS(-/-) db/db mice. In order to determine the role of elevated blood pressure per se versus additional deleterious effects of the renin-angiotensin system in mediation of disease progression, 8 week old eNOS(-/-) db/db mice were randomly divided into three groups: vehicle, treatment with the ACEI, captopril or treatment with "triple therapy" (hydralazine, resperine, HCTZ), and the animals were sacrificed after treatment for 12 wks. Blood pressure was reduced to comparable levels with ACE inhibition or "triple therapy". Although both treatment regimens decreased development of diabetic nephropathy, ACE inhibition led to more profound reductions in albuminuria, glomerulosclerosis, markers of tubulointerstitial injury, macrophage infiltration and markers of inflammation. Therefore, this animal model demonstrates conclusively that while there is an important role for blood pressure control, RAS blockade provides additional benefit in slowing the progression of diabetic nephropathy. |
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Authors:
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Ming-Zhi Zhang; Suwan Wang; Shilin Yang; Haichun Yang; Xiaofeng Fan; Takamune Takahashi; Raymond C Harris |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-23 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: - ISSN: 1522-1466 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Vanderbilt University School of Medicine. |
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