Large BP-dependent and -independent differences in susceptibility to nephropathy after nitric oxide inhibition in Sprague-Dawley rats from two major suppliers. Journal Article

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Authors: Griffin, K.; Polichnowski, A.; Licea-Vargas, H; Picken, M; Long, J; Williamson, G.; Bidani, A.
Article Title: Large BP-dependent and -independent differences in susceptibility to nephropathy after nitric oxide inhibition in Sprague-Dawley rats from two major suppliers.
Abstract: The N(omega)-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.
Journal Title: American Journal of Physiology - Renal Physiology
Volume: 302
Issue: 1
ISSN: 1522-1466
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: F173
End Page: 82
Language: English
DOI/URL:

http://ovidsp.ovid.com/ovidweb.cgi?T=JS=Y=N=fulltext=medl=21937607
Notes: ID: 12107; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: dks, 100901990; Other ID: Source: NLM. PMC3251341 [Available on 01/01/13]; CAS Registry/EC Number/Name of Substance: 0 (Nitrates). 0 (Nitrites). 10102-43-9 (Nitric Oxide). 50903-99-6 (NG-Nitroarginine Methyl Ester). EC 1-14-13-39 (Nitric Oxide Synthase).; Grant Number: DK-40426 (United States NIDDK NIH HHS), DK-61653 (United States NIDDK NIH HHS); Electronic Date of Publication: 20110921; Entry Date: 20120209