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The effects of lisinopril on the development of renal injury associated with prepubertal obesity
Author(s) -
Pennington Alyssa Paige,
McPherson Kasi,
Williams Jan
Publication year - 2017
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.31.1_supplement.883.15
Subject(s) - lisinopril , proteinuria , medicine , endocrinology , microalbuminuria , obesity , blood pressure , angiotensin converting enzyme , urology , kidney
Prepubertal childhood obesity has emerged as an epidemic and major health problem in the United States. Recent studies suggest that that childhood obesity is associated with increased risk of renal injury in children. Approximately 37% of obese children develop microalbuminuria. However, an understanding of the mechanisms involved in prepubertal obesity‐mediated renal disease remains unclear due to lack of an appropriate animal model. In studies characterizing the Dahl salt‐sensitive leptin receptor mutant (SS LepR mutant) rat, we observed that this model mimics several features of prepubertal obesity (PPO strain). Recently, we reported that the PPO strain displays proteinuria and podocyte injury as early as 6 weeks of age independent of hyperglycemia and elevations in arterial pressure. The standard care of treatment for children whom suffer from PPO is an angiotensin converting enzyme inhibitor (ACEi). Objective Therefore, in the current study, we examined whether treatment with lisinopril, an ACEi, prevents the early development of proteinuria in the PPO model. Methods Experiments were performed on six week‐old Control (lean) and PPO rats that were either treated with vehicle or lisinopril and measured proteinuria at 6, 8, and 10 weeks of age. Results At 6 weeks of age (baseline) proteinuria was significantly higher in the PPO strain versus the control rats (130±29 vs.14±3 mg/day, respectively). Treatment with lisinopril had no effect on the progression of proteinuria in control rats. However, lisinopril decreased proteinuria in PPO by 50%. Conclusion These data indicate that treatment with lisinopril slowed the progression of proteinuria in PPO rats and suggest that the renin‐angiotensin plays important role in the development of progression of proteinuria in this novel model of PPO. Support or Funding Information This work was supported by the APS STRIDE Summer Research Fellowship (1 R25 HL115473‐01) awarded to A.P. This work was also supported by an AHA SDG 12DG9440034 and by the National Institute of General Medical Sciences of the National Institutes of Health under Award number P20GM104357 awarded to J.M.W.