Related Experiment Videos
Captopril prevents nephropathy in HIV-transgenic mice
J E Bird1, S K Durham, M R Giancarli
1Division of Cardiovascular Drug Discovery, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA.
Journal of the American Society of Nephrology : JASN
|August 11, 1998
Summary
Captopril significantly reduced mortality and kidney damage in transgenic mice with HIV-associated nephropathy (HIVAN). This suggests ACE inhibition may be a key treatment for HIVAN, warranting further clinical trials.
Area of Science:
- Nephrology
- Virology
- Pharmacology
Background:
- Transgenic mice (T26) carrying HIV genes develop renal disease similar to human HIV-associated nephropathy (HIVAN).
- Previous studies suggest a role for the renin-angiotensin system in HIVAN pathogenesis.
Purpose of the Study:
- To investigate the therapeutic effects of captopril, an angiotensin-converting enzyme (ACE) inhibitor, on HIVAN in T26 mice.
- To evaluate captopril's impact on mortality, kidney function markers, and histological damage in a mouse model of HIVAN.
Main Methods:
- T26 and wild-type (WT) mice were treated with vehicle (VEH) or captopril (CAP) from 7 to 100 days of age.
- Mortality rates, urinary protein/creatinine ratio, blood urea nitrogen (BUN), glomerular injury, and tubulointerstitial injury were assessed.
Main Results:
- Captopril treatment significantly reduced mortality in T26 mice compared to VEH-treated T26 mice.
- CAP treatment normalized the elevated urinary protein/creatinine ratio in T26 mice.
- Glomerular and tubulointerstitial injury scores were markedly lower in CAP-treated T26 mice than in VEH-treated T26 mice.
Conclusions:
- Captopril effectively ameliorates renal disease in a mouse model of HIVAN.
- These findings support the hypothesis that ACE substrates are important mediators in HIVAN.
- A randomized placebo-controlled trial of captopril for HIVAN in patients is recommended.