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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2007.tde-11092007-130021
Document
Author
Full name
Flavio Teles de Farias Filho
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Zatz, Roberto (President)
Coimbra, Terezila Machado
Faria, José Butori Lopes de
Moyses, Rosa Maria Affonso
Vieira Junior, José Mauro
Title in Portuguese
Regressão da nefropatia diabética experimental: ausência de efeito dose-resposta de um antagonista da angiotensina II
Keywords in Portuguese
Diabetes Mellitus
Losartan/uso terapéutico
Nefropatias diabéticas
Ratos
Abstract in Portuguese
Nos últimos anos, evidências experimentais e clínicas tem sugerido a possibilidade de regressão de glomerulosclerose, em diversas formas de nefropatia progressiva, inclusive a diabética. No entanto, ainda não se sabe se lesões mais avançadas como glomerulosclerose acompanhada de sinéquias, podem ser revertidas com tratamento medicamentoso, ou se essa possibilidade só existe para lesões menos graves como expansão mesangial. Por outro lado, tem sido sugerido, recentemente, em diversas formas de nefropatia progressiva, que o efeito protetor dos bloqueadores do receptor AT-1 (BAT-1) é dose-dependente. Para avaliar a dose-dependência de um BAT-1 e a possibilidade de regressão de lesões glomerulares na nefropatia diabética (ND), ratos tornados diabéticos por estreptozotocina foram tratados com uma dose convencional e uma extremamente elevada de losartan (L). O tratamento com L reduziu a albuminúria e protegeu contra a glomerulosclerose e inflamação renal de forma semelhante com ambas as doses. Houve nítida regressão da expansão mesangial com o tratamento com L. Contudo, não foi observada regressão de glomerulosclerose. Os achados sugerem ausência de efeito protetor adicional com o uso de altas doses de L nesse modelo de ND. Os dados sugerem, ainda, que a regressão de lesões menos avançadas, como expansão de matriz mesangial, pode ser alcançada com o uso dos BAT-1 na ND.
Title in English
Regression of diabetic nephropathy : no dose-response effect of an angiotensin II antagonist
Keywords in English
Diabetes Mellitus
Diabetic nephropathies
Losartan/therapeutic use
Rats
Abstract in English
Evidence of regression of glomerulosclerosis in diabetic nephropathy (DN) and other modalities of chronic kidney diseases has been provided in recent years. However, it remains unclear whether advanced lesions such as glomerular sinechiae can be reversed with pharmacological therapy, or whether this possibility exists only for relatively moderate damage such as mesangial expansion. Recently, the protective renal effect of AT-1 receptor blockers (ARBs) was shown to be dose-dependent in chronic nephropathies. To verify whether an ARB possess a dose-dependent renal effect and whether glomerular lesions can regress in DN, rats were made diabetic by streptozotocin and treated with a standard and an extremely high dose of losartan (L). L treatment reduced albuminuria and protected against glomerulosclerosis and glomerular inflammation, without an additional effect with high doses. There was regression of mesangial expansion with L. However, there was no regression in the frequency of glomerulosclerosis with sinechiae. These findings suggest no dose-dependent effect of L in this model of DN and that mesangial matrix removal is a feasible aim with ARBs in DN.
 
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FlavioTFFilho.pdf (1.54 Mbytes)
Publishing Date
2007-09-17
 
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