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


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.


CONCLUSIONS
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.
Sari-Sarraf
Farid
F
Novartis Institutes for Biomedical Research, Inc., Cambridge, MA 02139, USA.
Pomposiello
Silvia
S
Laurent
Didier
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester