Renal Hemodynamic and Morphological Changes after 7 and 28 Days of Leptin Treatment: The Participation of Angiotensin II via the AT(1) Receptor

Autor(es)

Thieme, Karina ^[1] ; Oliveira-Souza, Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 3 MAR 20 2015.
• Citações Web of Science: 9

Resumo

The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT(1) receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan. Plasma leptin, Ang II and endothelin 1 (ET-1) levels were measured using an enzymatic immuno assay. The systolic blood pressure (SBP) was evaluated using the tail-cuff method. The renal plasma flow (RPF) and the glomerular filtration rate (GFR) were determined by p-aminohippuric acid and inulin clearance, respectively. Urinary Na+ and K+ levels were also analyzed. Renal morphological analyses, desmin and ED-1 immunostaining were performed. Proteinuria was analyzed by silver staining. mRNA expression of renin-angiotensin system (RAS) components, TNF-alpha and collagen type III was analyzed by quantitative PCR. Our results showed that leptin treatment increased Ang II plasma levels and progressively increased the SBP, achieving a pre-hypertension state. Rats treated with leptin 7 days showed a normal RPF and GFR, but increased filtration fraction (FF) and natriuresis. However, rats treated with leptin for 28 showed a decrease in the RPF, an increase in the FF and no changes in the GFR or tubular function. Leptin treatment-induced renal injury was demonstrated by: glomerular hypertrophy, increased desmin staining, macrophage infiltration in the renal tissue, TNF-a and collagen type III mRNA expression and proteinuria. In conclusion, our study demonstrated the progressive renal morphological changes in experimental hyperleptinemia and the interaction between leptin and the RAS on these effects. (AU)

• Processo FAPESP: 10/19656-5 - Estrutura e função renal na hipertensão e hiperleptinemia experimental: papel do sistema renina-angiotensina-aldosterona
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/19569-3 - Efeitos da endotelina 3 e da leptina na morfologia e função renal in vivo: participação do sistema renina-angiotensina intrarrenal
• Beneficiário: Maria Oliveira de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/23087-4 - Estudo molecular e funcional de transportadores de membrana
• Beneficiário: Gerhard Malnic
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/51117-7 - O tratamento com leptina por 7 e 28 dias altera a função e a morfologia renal de ratos
• Beneficiário: Karina Thieme
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 08/58287-5 - Estudo molecular e funcional de transportadores de ions em membranas
• Beneficiário: Gerhard Malnic
• Modalidade de apoio: Auxílio à Pesquisa - Temático