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Treatment with lisinopril slows the early progression of proteinuria in obese Dahl salt‐sensitive rats independent of lowering arterial pressure and GFR
Author(s) -
Pennington Alyssa P.,
Poudel Bibek P.,
Shields Corbin A.,
Thompson Willie,
Williams Jan M.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.573.3
Subject(s) - lisinopril , proteinuria , medicine , endocrinology , blood pressure , kidney disease , mean arterial pressure , renal function , ramipril , obesity , kidney , angiotensin converting enzyme , heart rate
Prepubertal childhood obesity (PPO) has emerged as an epidemic and major health problem in the United States. Previous studies have demonstrated that patients who developed obesity prior to puberty are at higher risk of developing progressive proteinuria and chronic kidney disease. Moreover, the early stages of renal injury associated with obesity is characterized with renal hyperfiltration. Recently, we observed the early development of renal injury in the obese Dahl salt‐sensitive leptin receptor mutant (SS LepR mutant) strain is associated with elevations in GFR. Furthermore, these renal abnormalities develop prior to puberty (6 weeks of age) and independent of hyperglycemia and elevations in arterial pressure. The standard care of treatment for obese children with hypertension and increased risk of renal disease is an angiotensin converting enzyme inhibitor (ACEi) such as lisinopril. Therefore, the current study examined whether treatment with lisinopril prevents the early development of proteinuria in the SS LepR mutant strain. Experiments were performed on four week‐old SS WT and SS LepR mutant rats that were either treated with vehicle or lisinopril (20 mg/kg/day, drinking water) for four weeks. We did not observe any differences in MAP between SS WT and SS LepR mutant rats (156±6 and 163±7 mmHg, respectively). While treatment with lisinopril markedly reduced MAP in SS WT rats (108±4 mmHg), lisinopril had no effect on MAP in the SS LepR mutant strain (146±7 mmHg). Proteinuria was significantly higher in the SS LepR mutant strain compared to SS WT rats at baseline (105±19 and 17±5 mg/day, respectively) and remained elevated over the course of the study (400±48 and 60±9 mg/day, respectively). Treatment with lisinopril significantly decreased the progression of proteinuria by 68% in SS WT rats (19±3 mg/day) and 40% in SS LepR mutant rats (242±31 mg/day). GFR was elevated in the SS LepR mutant strain compared to the values measured in the SS WT rats (4.80±0.50 vs. 3.87±0.48 mL/min, respectively). Interestingly, lisinopril treatment had no effect on GFR in both strains. These data suggest that obese SS LepR mutant rats develop progressive proteinuria associated with hypertension and elevations in GFR, and treatment with lisinopril blunted the progression of proteinuria independent of lowering GFR and arterial pressure during PPO. Support or Funding Information This work was supported by GM104357 and DK109133. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .