@entity8 is one of the major complications associated with the development of @entity101 . The objective of the present study was to determine whether and by which mechanisms treatment with @entity1809 receptor antagonists makes possible the regression of renal vascular and glomerular @entity82 . Experiments were performed in the @entity101 model of @entity842 (NO) deficiency in @entity35 . After 4 wk of @entity101 , mortality rates averaged 20%; the surviving animals displayed a decline of renal function (urine protein/ @entity1011 , 1.89 +/- 0.63 versus 0.24 +/- 0.03 mg/mmol; creatininemia, 110 +/- 14 versus 38 +/- 2 mmol/L in @entity101 animals and control, respectively; P < 0.01) and an exaggerated gene and protein expression of @entity1810 , collagen I, and collagen IV (P < 0.001) within the renal vasculature associated with the development of @entity631 ( @entity3808 index, 2.26 +/- 0.29 versus 0.12 +/- 0.04; P < 0.001). In addition, activities of matrix metalloproteinases 2 and 9 were increased twofold in renal vessels and glomeruli (P < 0.01). Afterwards, @entity9886 , an antagonist of @entity7774 receptor type I, or @entity2514 were administered in subgroups of @entity101 animals. After 1 wk of angiotensin II antagonism, collagen I, collagen IV, and @entity1810 gene and protein expressions were decreased and @entity631 was less marked ( @entity3808 index 1.04 +/- 0.45), whereas activities of metalloproteinases remained twofold higher than controls (P < 0.01). @entity2514 failed to improve renal function despite a similar degree of systolic pressure decrease. After 4 wk of @entity9886 , the renal functional and histologic parameters were completely normalized, whereas they remained damaged in the @entity101 animals in which the mortality rate reached 85%. These data suggest that the progression of @entity8 is a reversible process, at least in the @entity942 model. The mechanism of the regression appears to be dual: inhibition of collagen synthesis due to @entity1809 receptor antagonism and activation of metalloproteinases that is probably associated with the degree of @entity82 independently of @entity1809 blockade.

Regression of renal vascular and glomerular XXXX : role of angiotensin II receptor antagonism and matrix metalloproteinases.

@entity8 :: ('MESH:D007674', 'Disease') :: ['renal vascular fibrosis', 'Renal fibrosis'] @entity82 :: ('MESH:D005355', 'Disease') :: ['fibrosis'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension', 'hypertensive'] @entity7774 :: ('MESH:D000809', 'Chemical') :: ['angiotensin'] @entity1809 :: ('24180(Tax:10116)', 'Gene') :: ['AT1'] @entity2514 :: ('MESH:D006830', 'Chemical') :: ['hydralazine', 'Hydralazine'] @entity3808 :: ('MESH:C538213', 'Disease') :: ['sclerotic'] @entity9886 :: ('MESH:D019808', 'Chemical') :: ['losartan'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity1810 :: ('59086(Tax:10116)', 'Gene') :: ['TGF-beta'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity631 :: ('MESH:D005921', 'Disease') :: ['glomerulosclerosis'] @entity942 :: ('MESH:D003677', 'Disease') :: ['NO deficiency']
@entity82 :: (MESH:D005355,Disease) :: ['fibrosis']
