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Acute impairment of rat renal function by L -NAME as measured using dynamic MRI.

Sari-Sarraf, Farid and Pomposiello, Silvia and Laurent, Didier (2008) Acute impairment of rat renal function by L -NAME as measured using dynamic MRI. Magnetic Resonance Materials in Physics, Biology and Medicine, 21 (4). pp. 291-297. ISSN 0968-5243

Abstract

OBJECTIVE: To assess the feasibility of utilizing dynamic contrast enhanced (DCE)-MRI for depicting the effects of N (G)-nitro-L -arginine methylester (L -NAME), a nitric oxide synthase (NOS) inhibitor, on glomerular filtration rate (GFR) in rats. Since Gd-DTPA is mainly cleared through the kidneys, a first-order kinetic model was used to estimate GFR based on a clearance index (k ( cl )) that describes the tracer transport rate from the renal cortex to the outer medulla. MATERIALS AND METHODS: Normotensive Sprague-Dawley rats were infused with either vehicle (0.9% NaCl) or one of three doses of L -NAME (1, 3 or 10 mg/kg) for 30 min prior to imaging. In a separate set of animals, systolic blood pressure (SBP) was measured for all treatment groups. RESULTS: L -NAME caused a significant increase in SBP at all doses when compared to pre-dose values and at the two highest doses, post-infusion, when compared to vehicle. Administration of L -NAME also led to dose-dependent changes in the rate of Gd-DTPA uptake and tracer concentrations reached in selected regions of the kidney. The k ( cl ) measurements indicated a significant impairment of GFR following NOS blockade at the highest dose of L -NAME. CONCLUSION: DCE-MRI method detected changes in GFR in response to NO inhibition with L -NAME. This non-invasive technique could be used in longitudinal studies in preclinical and clinical settings offering a rapid assessment of single-kidney function.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: Glomerular filtration rate; Kidney; l-NAME; Rat; Magnetic resonance imaging
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Date Deposited: 14 Dec 2009 13:55
Last Modified: 31 Jan 2013 01:09
URI: https://oak.novartis.com/id/eprint/690

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