Abstract 492: Experimental Hyperleptinemia Induces Changes on Renal Function and Morphology in Rats
Aim: To evaluate the effect of experimental hyperleptinemia for 7 days and the participation of the Renin-Angiotensin II System (RAS) on renal function and morphology.
Methods: 40-days male Wistar rats were divided into 4 groups (n = 5 - 6 per group): sham (Sh), Leptin (Lep; s.c. infusion 0.5mg/kg/day, osmotic pump, Alzet), Losartan (Los; s.c. 10 mg/kg/day), Leptin plus Losartan (LL). Systolic blood pressure (SBP) was measured by tail-cuff method. On 8th day, rats were anesthetized and prepared to renal clearance experiments. Renal plasmatic flow (RPF) and glomerular filtration rate (GFR) were determined by p-Aminohippuric acid sodium and inulin clearance. Urinary NH4+, pH, Na+, K+ and osmolality were analyzed. Renal tissue was submitted to histological studies.
Results: 7-days Leptin treatment increased SBP (Sh: 105,8 ± 0,7 vs Lep: 118,0 ± 1,5 mmHg; *p<0.0001) and LL group reversed this parameter (LL: 103,4 ± 0,7 mmHg; *p<0.0001). Our preliminary results showed that Leptin and/or Losartan treatment does not affect renal hemodynamic (RPF - Sh: 20,48 ± 0,77 vs Lep: 15,79 ± 1,02 vs Los: 17,96 ± 2,21 vs LL: 18,99 ± 1,54 ml/min/kg and GFR - Sh: 7,94 ± 0,46 vs Lep: 9,19 ± 0,59 vs Los: 7,46 ± 0,60 vs LL: 6,97 ± 0,52 ml/min/kg). However, filtration fraction increased significantly in Lep group (Sh: 40,40 ± 1,72 vs Lep: 59,79 ± 2,46 %*; *p < 0.0001) and was corrected by Losartan (LL 34,42 ± 3,06 % #; # p< 0.0001). Urinary flux increased in Lep rats and was also corrected by Losartan (Sh: 0,18 ± 0,01 vs Lep: 0,25 ± 0,02; *p<0.001 vs LL: 0,18 ± 0,008#; #p< 0.0001 ml/min/kg). Na+ excretion, which had an 337% increase in Lep group, was normalized in LL. Urinary excretion of NH4+ and K+ and urinary osmolality was not different between the studied groups. All parameters of Los group were not statistically different from Sh rats. Lep rats showed an increase in total glomerular area, which was also corrected in LL rats (Sh: 6708 ± 62 vs Lep: 7796 ± 130 vs Los: 6779 ± 23 vs LL 6822 ± 20 μm2).
Discussion: Lep rats showed higher SBP, but not hypertension. Although there were no significant changes in renal hemodynamic, Leptin treatment caused glomerular hypertrophy. As many parameters were corrected by co-treatment with Losartan, it seems that RAS has a critical role in hyperleptinemic induced renal changes.
- © 2012 by American Heart Association, Inc.