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| Author(s): |
Junya de Lacorte Singulani
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Ribeirão Preto. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) |
| Defense date: | 2012-08-06 |
| Examining board members: |
Eduardo Barbosa Coelho;
Emmanuel de Almeida Burdmann;
Carlos Renato Tirapelli
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| Advisor: | Eduardo Barbosa Coelho |
| Abstract | |
Aldosterone is involved in the progression of renal disease in experimental models and clinical trials. Considering that the model of renovascular hypertension 2 kidney-1 clip (2K-1C) is characterized by a high activity of the renin-angiotensin-aldosterone system, the objective of this study was to assess the role of aldosterone in renal injury in this model by blocking the mineralocorticoid receptor (MR) with spironolactone. Male Wistar rats were submitted to surgery to place a silver clip on the left renal artery and after two weeks of the development of 2K-1C renovascular hypertension they were divided into three groups. The first group was administered no drug (n=8), in the second group spironolactone 20 mg/kg/day was given orally (n=10) and the third group received amiloride 7 mg/kg/day (n=12). Body weight and systolic blood pressure were monitored weekly. Samples of urine (collected for 24 h) and blood were performed in 3 distinct periods: before surgery; 2 weeks after surgery (before treatment) and 6 weeks after surgery (after treatment). The samples were used to analyze creatinine, osmolality, sodium, potassium and albuminuria. At the end of the experiment, the kidneys were perfused and weighed. Histological analysis to assess the extent of tubulointerstitial changes was performed. Additionally, markers of inflammation (ED-1 and p-JNK), production of extracellular matrix (fibronectin), myofibroblasts (-smooth muscle actin) and tubular transdifferentiation (vimentin) in the area of tubulointerstitial cortical and injury in podocytes (desmin) were evaluated. Treatment with spironolactone was able to attenuate the increase in albumin excretion, the increase in plasma concentration of creatinine and the reduction in creatinine clearance. In the clipped kidney, tubulointerstitial and podocytes injuries, demonstrated by markers studied, were discrete and therapy with spironolactone or amiloride was not able to minimize them. However, in the non-clipped kidney, administration of spironolactone attenuated the increase of extracellular matrix and podocyte injury. The beneficial effects of spironolactone occurred independent of the reduction blood pressure and can be partly dependent of epithelial sodium channel (ENaC) blockade. These effects bring perspective to espironolactone as a therapeutic tool to be explored in patients with renal artery stenosis. (AU) | |
| FAPESP's process: | 11/02792-6 - Role of aldosterone in the development of tubulointerstitial lesions in hypertensive rats 2R-1C |
| Grantee: | Junya de Lacorte Singulani |
| Support Opportunities: | Scholarships in Brazil - Master |