Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy Journal Article

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Authors: Polichnowski, A. J.; Licea-Vargas, H; Picken, M. M.; Long, J; Bisla, R.; Williamson, G. A.; Bidani, A. K.; Griffin, K. A.
Article Title: Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy
Abstract: The diet-induced obesity (DIO) model is frequently employed to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 months. In the present study, we investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. 8-week old male obesity prone (OP) and obesity resistant (OR) rats (Charles River) were administered a moderately high fat (MHF) diet for 5 months. Radiotelemetrically-measured blood pressure (BP), proteinuria and GS were assessed. OP (n=10) rats developed modest hypertension (142+/-3 vs. 128+/-2 mmHg, P0.05) and substantial levels of proteinuria (63+/-12 vs. 12+/-1 mg/day, P0.05) and GS (7.7+/-1.4 vs. 0.4+/-0.2 %) vs. OR rats (n=8). Potential hemodynamic mechanisms of renal injury were assessed in additional groups of OP and OR rats fed a MHF diet for 3 months. Kidney weight (4.3+/-0.2 vs. 4.3+/-0.1 grams), glomerular filtration rate (3.3+/-0.3 vs. 3.1+/-0.1 ml/min), and glomerular volume (1.9+/-0.1 vs. 2.0+/-0.1 microm3x10-6) were similar between OP (n=6) and OR (n=9) rats. Renal blood flow (RBF) autoregulation was also similar in OP (n=7) and OR (n=7) rats. In contrast, Nomega-nitro-L-arginine methyl ester (L-NAME) administration in conscious, chronically instrumented OP (n=11) rats resulted in a 15% and 39% increase in BP and renal vascular resistance, respectively, and a 16% decrease in RBF. Minimal effects of L-NAME were seen in OR (n=9) rats. In summary, DIO-associated GS is preceded by an increased hemodynamic sensitivity to L-NAME, but not renal hypertrophy or hyperfiltration.
Journal Title: American journal of physiology.Renal physiology
ISSN: 1522-1466; 1522-1466
Publisher: American Journal of Physiology - Renal Physiology  
Date Published: 2015
Start Page: ajprenal.00211.2015
Language: ENG
DOI/URL:

10.1152/ajprenal.00211.2015
Notes: LR: 20150626; CI: Copyright (c) 2015; JID: 100901990; OTO: NOTNLM; aheadofprint; SO: Am J Physiol Renal Physiol. 2015 Jun 24:ajprenal.00211.2015. doi: 10.1152/ajprenal.00211.2015.