Candesartan prevents the progression of mesangioproliferative nephritis in rats.
We previously reported a new animal model of progressive glomerulonephritis induced by a single intravenous injection of the anti-Thy-1 monoclonal antibody MoAb 1-22-3 into uninephrectomized rats (Clin Exp Immunol 102: 181-185, 1995). We examined the effects of angiotensin II (Ang II) receptor antagonist (candesartan) on the clinical features and morphological lesions of this new model. By 10 weeks after induction of nephritis, untreated rats had developed hypertension, massive proteinuria, renal dysfunction, and severe glomerular injury, while uninephrectomized control rats had not. There was a significant increase in levels of glomerular protein and cortical mRNA for transforming growth factor-beta (TGF-beta) and type I and type III collagens in untreated nephritic rats. Ten week treatments with candesartan and hydralazine significantly reduced blood pressure (BP) to an equal extent. Candesartan, but not hydralazine, prevented proteinuria, normalized renal function, and ameliorated glomerular injury. Candesartan also reduced levels of glomerular protein and cortical mRNA for TGF-beta and type I and type III collagens, while hydralazine did not. These findings suggest that candesartan prevents progression to end-stage renal failure by modulating the effects of Ang II at least in part on the production of TGF-beta and type I and type III collagens, and not merely on systemic BP.
Nakamura
T
T
Department of Internal Medicine, Yamanashi Medical University, Japan.
Obata
J
J
Onizuka
M
M
Kimura
H
H
Ohno
S
S
Yoshida
Y
Y
Kawachi
H
H
Shimizu
F
F
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000473:pathology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000473:pathology; D011507:Proteinuria / Q000188:drug therapy / Q000652:urine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013777:Tetrazoles; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D003094:Collagen; C077793:candesartan cilexetil