Angiotensin blockade and matrix synthesis by glomerular epithelial cells in high glucose: a further experimental insight into the pathophysiology of diabetic nephropathy.
OBJECTIVE
Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor-1 (AT-1) antagonists are used in the treatment of proteinuria of diabetic nephropathy. One of the major pathogenic events in this condition is represented by the alteration of the extracellular matrix protein synthesis by glomerular epithelial cells.


METHODS
We evaluated the effects of the angiotensin converting enzyme inhibitor, Enalaprilat, and the AT-1 receptor antagonist, Losartan, on mRNA fibronectin and laminin synthesis by glomerular epithelial cells, in conditions mimicking hyperglycemia.


RESULTS
In high glucose conditions, Enalaprilat reduced significantly the mRNA expression of fibronectin (p 0.03), but not significantly that of laminin. Losartan addition to high glucose incubated cells reduced (-30%) mRNA expression of fibronectin, and significantly (p 0.05) the mRNA expression of laminin.


CONCLUSIONS
In addition to the known hemodynamic effects, the improvement of renal function in diabetic patients treated with these compounds may also be due to a modulator effect on extracellular matrix content and composition.
Morano
S
S
Department of Clinical Sciences, Endocrinology, Clinica Medica 2, La Sapienza University, Rome, Italy. susanna.morano@uniroma1.it
Cipriani
R
R
Santangelo
C
C
Fallarino
M
M
Carnovale
A
A
Mandosi
E
E
Gatti
A
A
Sensi
M
M
Di Mario
U
U
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000503:physiopathology*; D015773:Enalaprilat / Q000494:pharmacology* / Q000627:therapeutic use; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D006943:Hyperglycemia / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology*; D007797:Laminin / Q000096:biosynthesis* / Q000235:genetics; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D015773:Enalaprilat; D019808:Losartan