| Authors |
Zhang MZ, Wang S, Yang S, Yang H, Fan X, Takahashi T, Harris RC
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| Submitted By |
Raymond Harris on 2/22/2012 |
| Status |
Published |
| Journal |
American journal of physiology. Renal physiology |
| Year |
2012 |
| Date Published |
2/1/2012 |
| Volume : Pages |
302 : F433 - F438 |
| PubMed Reference |
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| Abstract |
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. To determine the role of elevated blood pressure per se
vs. additional deleterious effects of the RAS in mediation of disease
progression, 8-wk-old eNOS(-/-) db/db mice were randomly divided into three
groups: vehicle, treatment with the angiotensin-converting enzyme inhibitor
(ACEI) captopril, or treatment with "triple therapy" (hydralazine, resperine,
hydrocholorothiazide), and the animals were euthanized after treatment for 12
wk. 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 suggests that while there is an important role for blood pressure control,
RAS blockade provides additional benefits in slowing the progression of diabetic
nephropathy.
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