ACE inhibitors improve nephrin expression in Zucker rats with glomerulosclerosis.
BACKGROUND
Podocyte injury is associated with many forms of human and experimental proteinuric glomerular disease. The aim of this study was to investigate the level of nephrin expression in a model of obesity and type II diabetes mellitus, the obese Zucker rat, as well as to investigate whether nephrin expression is influenced by treatment with quinapril or diltiazem, 2 drugs frequently used in type II diabetes mellitus.


METHODS
Obese Zucker rats were treated with either quinapril or diltiazem at a dose of 10 mg/kg body weight per day and 100 mg/kg body weight per day, respectively, for 6 months. Real time reverse transcription-polymerase chain reaction (RT-PCR) and immunoperoxidase assays were used to assess and quantify nephrin gene expression and other markers of podocyte damage, such as desmin and synaptopodin protein.


RESULTS
Quinapril treatment prevented the reduction of nephrin levels compared with the control group, while diltiazem treatment did not prevent the reduction. Similar results were obtained when other phenotypic markers, such as desmin, were assessed. Similarly, synaptodin showed this tendency, although it did not achieve statistically significant differences.


CONCLUSIONS
The podocyte phenotypic changes assessed in a model of obesity and type II diabetes mellitus were corrected by an angiotensin-converting enzyme (ACE) inhibitor. These results could be associated with an improvement in the slit diaphragm, and therefore, in the maintenance of the filtration barrier. Diltiazem did not achieve similar results.
Blanco
Sandra
S
Departments of Nephrology and Pathology, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Bonet
Josep
J
López
Dolores
D
Casas
Irma
I
Romero
Ramón
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D003893:Desmin / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D008297:Male; D008565:Membrane Proteins; D008840:Microfilament Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D000077583:Quinapril; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D018076:DNA, Complementary; D003893:Desmin; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; C503967:SYNPO protein, human; C503969:Synpo protein, rat; D044005:Tetrahydroisoquinolines; C113267:nephrin; D012313:RNA; D004110:Diltiazem; D000077583:Quinapril