Effects of AT1 receptor antagonist on proteoglycan gene expression in hypertensive rats

Proteoglycans are an important component of the extracellular matrix, and a re thought to play multiple roles not only in kidney remodeling, but also i n regulating glomerular permeability, and in modulating the activity of oth er cytokines and growth factors. The aim of this study was to examine the g ene expressions of proteoglycan core proteins in hypertensive rat kidneys, and their modulation by AT1 receptor antagonist, SHRSP/lzm rats and normote nsive control WKY/lzm rats on a normal salt diet were treated with or witho ut 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 exc ised, and gene expressions of the proteoglycan core proteins versican, perl ecan, decorin, and biglycan were examined by Northern blot analysis and RT- PCR. Treatment with candesartan cilexetil caused significant decreases in b lood pressure and amelioration of proteinuria and renal histological scores in the SHRSP/lzm rats. Compared to WKY/lzm rats, expression of biglycan mR NA showed a small increase in SHRSP/lzm rats which did not attain statistic al significance. On the other hand, treatment with candesartan caused signi ficant reductions in biglycan and decorin mRNA in the SHRSP/lzm rats, In co ntrast, the level of versican mRNA appeared to be increased after candesart an treatment. These results suggest that treatment with AT1 receptor antago nist was associated with diverse changes in renal proteoglycan gene express ion in SHRSP/lzm rats. These changes could contribute to the beneficial eff ects of AT1 receptor antagonist on tissue remodeling and inhibition of dise ase progression in hypertensive rat kidneys.