Early renal abnormalities in a experimental model that combind genetic arterial hypertension and diabetes mellitus : effect of anty-hypertensive treatment / Alterações renais precoces em um modelo experimental que combina hipertensão arterial genetica e diabetes mellitus : efeitos do tratamento anti-hipertensivo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

In diabetic patients hypertension is the main secondary factor associated with the development and progression of renal disease. However, the mechanism of interaction between diabetes and hypertension to exacerbate diabetic renal disease is poorly understood. The aim of this study was to evaluate the effect of presence of hypertension had on nephrin expression, glomerular hypertrophy, renal celI replication and accumulation of glomerular TGF f3 and fibronectin in a model of genetic hypertension and experimental diabetes mellitus. Four-week-old spontaneously hypertensive rats (SHR) and their normotensive control Wistar K yoto (WKY) were rendered diabetic by means of intravenously injection of streptozotocin. To further assess the contribution ofhypertension to renal abnormalities diabetic SHR were randomÍzed for no treatment, or for treatment with captopril, losartan or triple therapy (hydrochlorothiazide, reserpine and hydralazine) for 20 days. Increase in systolic blood pressure was equally prevented by captopril (113 :i: 9mmHg), losartan (115 :!:: 16) and triple therapy (108 :i: 12, p<0.005). Glomerular expression of nephrin was reduced in SHR and further diminished in diabetic SHR in comparison with controls and the antihypertensive treatment prevents the reduction in glomerular expression of nephrin. Glomerular sÍze was higher (p<0.005) in diabetic SHR (27,300 :i: 2130 Jim2) compared with non-diabetic SHR (23,800 :!:: 307). The antihypertensive therapy with captopril (23,900 :i: 175), losartan (23,800 :i:120), and triple therapy (23,400 :i:21O) prevented the glomerular enlargement in diabetic SHR. Glomerular expression of TGF f3 and fibronectin was significantly increased in diabetic SHR as compared to the controls, and was prevented with captopril, losartan and triple therapy. The number of replicating glomerular cell significantly decreased in diabetic SHR and it was restored by alI three antihypertensive regimes. The glomerular expression of p27Kipl was significantly higher in diabetic SHR but it was not modified by antihypertensive treatment. In diabetic rats the presence of genetic hypertension induced early renal abnormalities that were prevented by strict control of blood pressure. These abnormalities may be involved in the mechanism of interaction between diabetes and hypertension to exacerba te renal disease

ASSUNTO(S)

diabetes mellitus inibidores da enzima conversora da angiotensina inhibitors nefropatias diabeticas diabetes arterial hypertension angiotensin converting enzyme diabetic nephropathy hipertensão arterial

ACESSO AO ARTIGO

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