Effects of AT1 receptor antagonist on proteoglycan gene expression in hypertensive rats.
Proteoglycans are an important component of the extracellular matrix, and are thought to play multiple roles not only in kidney remodeling, but also in regulating glomerular permeability, and in modulating the activity of other cytokines and growth factors. The aim of this study was to examine the gene expressions of proteoglycan core proteins in hypertensive rat kidneys, and their modulation by AT1 receptor antagonist. SHRSP/Izm rats and normotensive control WKY/Izm rats on a normal salt diet were treated with or without the AT1 receptor antagonist candesartan cilexetil (1 mg/kg/day) from 10 weeks to 22 weeks. At the end of the treatment period, renal tissue was excised, and gene expressions of the proteoglycan core proteins versican, perlecan, decorin, and biglycan were examined by Northern blot analysis and RT-PCR. Treatment with candesartan cilexetil caused significant decreases in blood pressure and amelioration of proteinuria and renal histological scores in the SHRSP/Izm rats. Compared to WKY/Izm rats, expression of biglycan mRNA showed a small increase in SHRSP/Izm rats which did not attain statistical significance. On the other hand, treatment with candesartan caused significant reductions in biglycan and decorin mRNA in the SHRSP/Izm rats. In contrast, the level of versican mRNA appeared to be increased after candesartan treatment. These results suggest that treatment with AT1 receptor antagonist was associated with diverse changes in renal proteoglycan gene expression in SHRSP/Izm rats. These changes could contribute to the beneficial effects of AT1 receptor antagonist on tissue remodeling and inhibition of disease progression in hypertensive rat kidneys.
Sasamura
H
H
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Shimizu-Hirota
R
R
Nakaya
H
H
Saruta
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D058578:Biglycan; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology; D037181:Lectins, C-Type; D008297:Male; D009400:Nephrosclerosis / Q000188:drug therapy / Q000503:physiopathology; D011509:Proteoglycans / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D053675:Versicans
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; C546886:Bgn protein, rat; D058578:Biglycan; D001713:Biphenyl Compounds; D011508:Chondroitin Sulfate Proteoglycans; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D037181:Lectins, C-Type; D011509:Proteoglycans; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; C508324:Vcan protein, rat; D053675:Versicans; C071927:perlecan; C077793:candesartan cilexetil