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(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.
authors.affiliation: Department of Medicine, Loyola Univ. Chicago, 2160 S. First Ave., Maywood, IL 60153, USA. kgriffi@lumc.edu
authors.forename: Karen
authors.initials: K
authors.lastname: Griffin
authors.forename: Aaron
authors.initials: A
authors.lastname: Polichnowski
authors.forename: Hector
authors.initials: H
authors.lastname: Licea-Vargas
authors.forename: Maria
authors.initials: M
authors.lastname: Picken
authors.forename: Jianrui
authors.initials: J
authors.lastname: Long
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Williamson
authors.forename: Anil
authors.initials: A
authors.lastname: Bidani
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000139:chemically induced*; D007674:Kidney Diseases / Q000139:chemically induced*; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009392:Nephrectomy; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester