Effects of dehydroepiandrosterone and quinapril on nephropathy in obese Zucker rats.
BACKGROUND
The obese Zucker rat exhibits insulin resistance, develops nephropathy at an early age, and may be a model of diabetic nephropathy. Dehydroepiandrosterone (DHEA) may ameliorate many of the factors that contribute to diabetic nephropathy, while angiotensin-converting enzyme inhibitors are known to be effective. One marker of nephropathy is the expression of alpha-smooth muscle actin.


METHODS
We studied the effect of DHEA on the expression of alpha-smooth muscle actin in obese Zucker rats and compared the changes with those in a control group, a group given quinapril, and a group on a low-calorie diet. DHEA (0.6%) added to plain chow, quinapril (0.3 mg/kg) added to drinking water, and a low-calorie diet based on pair-feeding were administered to obese rats from age 4 to 20 weeks. Immunohistochemical expression of alpha-smooth muscle actin, a marker of interstitial and glomerular fibrosis and an early indicator of nephropathy, was measured semiquantitatively in glomeruli, cortical interstitium, and medullary interstitium on a scale of 0 to 4 and was reported as mean +/- SEM.


RESULTS
When compared with the obese control group, quinapril exhibited a marked reduction in alpha-smooth muscle actin staining in glomeruli, cortical interstitium, and medullary interstitium (P < 0.0005); DHEA reduced alpha-smooth muscle actin staining in cortical interstitium and medullary interstitium (P < 0. 005), and a low-calorie diet reduced alpha-smooth muscle actin staining in cortical and medullary interstitium (P < 0.005), which was similar to the effects of DHEA.


CONCLUSIONS
DHEA was similar to a low-calorie diet in reducing the immunohistochemical staining of alpha-smooth muscle actin in obese Zucker rats. However, quinapril exerted a marked protective effect on the development of fibrosis, as indicated by alpha-smooth muscle actin staining, which was significantly less than that of DHEA at the doses studied.
Richards
R J
RJ
Section of Endocrinology and Section of Nephrology, Department of Medicine, and Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112-2822, USA. richards@lsuhsc.edu
Porter
J R
JR
Inserra
F
F
Ferder
L F
LF
Stella
I
I
Reisin
E
E
Svec
F
F
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000419:Albuminuria; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D000077583:Quinapril; D051381:Rats; D011924:Rats, Zucker / Q000502:physiology*; D044005:Tetrahydroisoquinolines; D013851:Thinness; D014018:Tissue Distribution
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D003687:Dehydroepiandrosterone; D003404:Creatinine; D000077583:Quinapril