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Renal hemodynamic and morphological changes after 7 and 28 days of leptin treatment: the participation of angiotensin II via the AT1 receptor.

Thieme K, Oliveira-Souza M - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

ABSTRACT
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 AT1 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-α 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-α 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.

No MeSH data available.


Related in: MedlinePlus

Desmin staining.Renal desmin immunostaining of the rats treated for 7 (A-D) and 28 days (E-H), ×20. Arrowheads = desmin staining; bar = 50 μm. For the rats treated for 7 days: sham (n = 6); losartan (n = 6); leptin (n = 6); and leptin plus losartan (n = 6). For the rats treated for 28 days: sham (n = 6); losartan (n = 6), leptin (n = 8); leptin plus losartan (n = 6).
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pone.0122265.g005: Desmin staining.Renal desmin immunostaining of the rats treated for 7 (A-D) and 28 days (E-H), ×20. Arrowheads = desmin staining; bar = 50 μm. For the rats treated for 7 days: sham (n = 6); losartan (n = 6); leptin (n = 6); and leptin plus losartan (n = 6). For the rats treated for 28 days: sham (n = 6); losartan (n = 6), leptin (n = 8); leptin plus losartan (n = 6).

Mentions: Although Gunduz et al.[18] showed an increase in TGF-β staining in the rats treated with leptin for 28 days, no studies have demonstrated glomerular injury in experimental hyperleptinemia. Our results showed that, along with glomerular hypertrophy, the rats treated with leptin for 7 and 28 days qualitatively exhibited increased desmin expression, as indicated by the arrowheads in Fig. 5A-H. In the leptin plus losartan group, the staining was decreased, indicating the contribution of Ang II, via the AT1 receptors, in the glomerular injury. Because the effects of leptin were more pronounced in the rats treated for 28 days, we also performed additional immunohistochemical studies for ED-1 (CD68). The anti-CD68 antibody used reacts to a cytoplasmic antigen present both in monocytes and macrophages [39]. Thus, ED-1 staining is a good marker of macrophage infiltration in the tissue. Our results showed a significant increase in this cell type in the cortical tubulointerstitium from the rats treated with leptin (in positive cells/field: sham = 10.75 ± 1.38; losartan = 7.5 ± 0,64; leptin = 92.5 ± 9.39* and leptin plus losartan = 31.75 ± 2.17#$; *p<0.05 versus the sham group; #p<0.05 versus the leptin-treated rats and $p<0.05 versus the losartan group) (Fig. 6A-D).


Renal hemodynamic and morphological changes after 7 and 28 days of leptin treatment: the participation of angiotensin II via the AT1 receptor.

Thieme K, Oliveira-Souza M - PLoS ONE (2015)

Desmin staining.Renal desmin immunostaining of the rats treated for 7 (A-D) and 28 days (E-H), ×20. Arrowheads = desmin staining; bar = 50 μm. For the rats treated for 7 days: sham (n = 6); losartan (n = 6); leptin (n = 6); and leptin plus losartan (n = 6). For the rats treated for 28 days: sham (n = 6); losartan (n = 6), leptin (n = 8); leptin plus losartan (n = 6).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368722&req=5

pone.0122265.g005: Desmin staining.Renal desmin immunostaining of the rats treated for 7 (A-D) and 28 days (E-H), ×20. Arrowheads = desmin staining; bar = 50 μm. For the rats treated for 7 days: sham (n = 6); losartan (n = 6); leptin (n = 6); and leptin plus losartan (n = 6). For the rats treated for 28 days: sham (n = 6); losartan (n = 6), leptin (n = 8); leptin plus losartan (n = 6).
Mentions: Although Gunduz et al.[18] showed an increase in TGF-β staining in the rats treated with leptin for 28 days, no studies have demonstrated glomerular injury in experimental hyperleptinemia. Our results showed that, along with glomerular hypertrophy, the rats treated with leptin for 7 and 28 days qualitatively exhibited increased desmin expression, as indicated by the arrowheads in Fig. 5A-H. In the leptin plus losartan group, the staining was decreased, indicating the contribution of Ang II, via the AT1 receptors, in the glomerular injury. Because the effects of leptin were more pronounced in the rats treated for 28 days, we also performed additional immunohistochemical studies for ED-1 (CD68). The anti-CD68 antibody used reacts to a cytoplasmic antigen present both in monocytes and macrophages [39]. Thus, ED-1 staining is a good marker of macrophage infiltration in the tissue. Our results showed a significant increase in this cell type in the cortical tubulointerstitium from the rats treated with leptin (in positive cells/field: sham = 10.75 ± 1.38; losartan = 7.5 ± 0,64; leptin = 92.5 ± 9.39* and leptin plus losartan = 31.75 ± 2.17#$; *p<0.05 versus the sham group; #p<0.05 versus the leptin-treated rats and $p<0.05 versus the losartan group) (Fig. 6A-D).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

ABSTRACT
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 AT1 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-α 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-α 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.

No MeSH data available.


Related in: MedlinePlus