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Molecular mechanisms associated to reversion of proteinuria by RAS antagonists in renovascular hypertensive rats (1088.4)
Author(s) -
Correa Jose,
Girardi Adriana,
Salles Thiago,
Boaro Karoline,
Loredo Felipe,
Yogi Alvaro,
Callera Glaucia,
Touyz Rhian,
Bendhack Lusiane,
Krieger Jose
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1088.4
Subject(s) - losartan , enalapril , medicine , endocrinology , proteinuria , albuminuria , angiotensin ii , hydralazine , blood pressure , angiotensin ii receptor type 1 , angiotensin converting enzyme , kidney
The present work aimed to compare the effects of monotheraphy versus combined therapy of enalapril and losartan and investigate the mechanisms by which these antihypertensive agents revert proteinuria in 2K‐1C hypertensive rats. To this end, male Wistar rats were subjected to 2K‐1C surgery or sham‐operation (2K). After six weeks, rats were treated with losartan (30mg/Kg/day), enalapril (20mg/Kg/day), losartan+enalapril (20+30mg/Kg/day) or saline by gavage for 14 days. Systolic blood pressure (SBP, mmHg) was higher in 2K‐1C (247±5) than in 2K (129±2, P<0.0001). Losartan (197±6, P<0.05) and enalapril (205±7, n=8, P<0.05) progressively reduced 2K‐1C SBP, with an additional hypotensive effect in the group treated with both drugs (173±16mmHg, P<0.001). Plasma levels of Ang II and TBARS were similar in 2K and 2K‐1C rats and were not changed by the treatments. Albuminuria was remarkably increased in 2K‐1C control rats when compared to 2K control rats. Treatment of 2K‐1C rats with losartan and enalapril similarly reduced albumin excretion when compared to the untreated 2K‐1C. A more pronounced reduction of albuminuria was observed in rats treated with combined therapy. Lucigenin‐derived chemiluminescence was not different in the right and left kidneys of 2K and 2K‐1C rats. Treatments had no effect upon NADPH oxidase activity. The expression of glomerular proteins, including nephrin and podocin, and of proximal tubular protein such as megalin and the Cl/H+ exchanger ClC‐5 were much lower in 2K1C compared to 2K. Treatment with enalapril or losartan partially reverted whereas combined therapy completely restored the expression levels of nephrin and podocin. Taken together, these results suggest that the antiproteinuric effects induced by RAS inhibitors in 2K‐1C rats does not involve inhibition of ROS, but is associated with normalization of the expression of nephrin and podocin in the glomeruli. Grant Funding Source : Supported by FAPESP, CAPES, CNPq, CIHR and Heart and Stroke Foundation of Canada.