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Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Renal+Physiol 2015 ; 309 (9): F791-9 Nephropedia Template TP
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Glomerulosclerosis in the diet-induced obesity model correlates with sensitivity to nitric oxide inhibition but not glomerular hyperfiltration or hypertrophy #MMPMID26109088
Polichnowski AJ; Licea-Vargas H; Picken M; Long J; Bisla R; Williamson GA; Bidani AK; Griffin KA
Am J Physiol Renal Physiol 2015[Nov]; 309 (9): F791-9 PMID26109088show ga
The diet-induced obesity (DIO) model is frequently used to examine the pathogenesis of obesity-related pathologies; however, only minimal glomerulosclerosis (GS) has been reported after 3 mo. We investigated if GS develops over longer periods of DIO and examined the potential role of hemodynamic mechanisms in its pathogenesis. Eight-week-old male obesity-prone (OP) and obesity-resistant (OR) rats (Charles River) were administered a moderately high-fat diet for 5 mo. Radiotelemetrically measured blood pressure, proteinuria, and GS were assessed. OP (n = 10) rats developed modest hypertension (142 ± 3 vs. 128 ± 2 mmHg, P < 0.05) and substantial levels of proteinuria (63 ± 12 vs. 12 ± 1 mg/day, P < 0.05) and GS (7.7 ± 1.4% vs. 0.4 ± 0.2%) compared with OR rats (n = 8). Potential hemodynamic mechanisms of renal injury were assessed in additional groups of OP and OR rats fed a moderately high-fat diet for 3 mo. Kidney weight (4.3 ± 0.2 vs. 4.3 ± 0.1 g), 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 ?m3 × 10?6) were similar between OP (n = 6) and OR (n = 9) rats. Renal blood flow autoregulation was preserved in both OP (n = 7) and OR (n = 7) rats. In contrast, N?-nitro-l-arginine methyl ester (l-NAME) administration in conscious, chronically instrumented OP (n = 11) rats resulted in 15% and 39% increases in blood pressure and renal vascular resistance, respectively, and a 16% decrease in renal blood flow. 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.