Sprague-Dawley rats from Harlan exhibited significant glomerular injury (12%) and proteinuria after L-NAME administration, whereas Charles River rats were completely resistant to nephropathy despite developing moderate hypertension.
Sprague-Dawley rats from different suppliers exhibit strikingly large, blood pressure-independent differences in susceptibility to l-NAME-induced nephropathy, highlighting the importance of genetic background in preclinical models.
Tasa de eventos absoluta: 12% vs 0%
valor p: p=<0.0001
The N(ω)-nitro-l-arginine methyl ester (l-NAME) model is widely employed to investigate the role of nitric oxide (NO) in renal injury. The present studies show that Sprague-Dawley rats from Harlan (H) and Charles River (CR) exhibit strikingly large differences in susceptibility to l-NAME nephropathy. After 4 wk of l-NAME (∼50 mg·kg(-1)·day(-1) in drinking water), H rats (n = 13) exhibited the expected hypertension average radiotelemetric systolic blood pressure (BP), 180 ± 3 mmHg, proteinuria (136 ± 17 mg/24 h), and glomerular injury (GI) (12 ± 2%). By contrast, CR rats developed less hypertension (142 ± 4), but surprisingly no proteinuria or GI, indicating a lack of glomerular hypertension. Additional studies showed that conscious H, but not CR, rats exhibit dose-dependent renal vasoconstriction after l-NAME. To further investigate these susceptibility differences, l-NAME was given 2 wk after 3/4 normotensive nephrectomy (NX) and comparably impaired renal autoregulation in CR-NX and H-NX rats. CR-NX rats, nevertheless, still failed to develop proteinuria and GI despite moderate hypertension (144 ± 2 mmHg, n = 29). By contrast, despite an 80-90% l-NAME dose reduction and lesser BP increases (169 ± 4 mmHg), H-NX rats (n = 20) developed greater GI (26 ± 3%) compared with intact H rats. Linear regression analysis showed significant (P < 0.01) differences in the slope of the relationship between BP and GI between H-NX (slope 0.56 ± 0.14; r = 0.69; P < 0.008) and CR-NX (slope 0.09 ± 0.06; r = 0.29; P = 0.12) rats. These data indicate that blunted BP responses to l-NAME in the CR rats are associated with BP-independent resistance to nephropathy, possibly mediated by a resistance to the renal (efferent arteriolar) vasoconstrictive effects of NO inhibition.
Griffin et al. (Thu,) conducted a other in L-NAME induced nephropathy and hypertension (n=94). L-NAME (N-omega-nitro-L-arginine methyl ester) vs. Charles River strain (strain comparison) was evaluated on Glomerular injury (p=<0.0001). Sprague-Dawley rats from Harlan exhibited significant glomerular injury (12%) and proteinuria after L-NAME administration, whereas Charles River rats were completely resistant to nephropathy despite developing moderate hypertension.