title: Assessment of impaired vascular reactivity in a rat model of diabetic nephropathy: effect of nitric oxide synthesis inhibition on intrarenal diffusion and oxygenation measured by magnetic resonance imaging.
abstract: Diabetes is associated with impaired vascular reactivity and the development of diabetic nephropathy. In a rat model of streptozotocin-induced diabetic nephropathy, the effects of systemic nitric oxide (NO) synthesis inhibition on intrarenal diffusion and oxygenation were determined by noninvasive magnetic resonance diffusion tensor imaging and blood O2 level-dependent (BOLD) imaging, respectively. Eight weeks after the induction of diabetes, 21 rats [n = 7 rats each in the untreated control group, diabetes mellitus (DM) group, and DM with uninephrectomy (DM UNX) group] were examined by MRI. Diffusion tensor imaging and BOLD sequences were acquired before and after NO synthesis inhibition with N-nitro-L-arginine methyl ester (L-NAME). In the same rats, mean arterial pressure and vascular conductance were determined with and without the influence of L-NAME. In control animals, NO synthesis inhibition was associated with a significant increase of mean arterial pressure of 33.8 ± 4.3 mmHg (P < 0.001) and a decrease of vascular conductance of -17.8 ± 2.0 μl·min(-1)·100 mmHg(-1) (P < 0.001). These changes were attenuated in both DM and DM UNX groups with no significant difference between before and after L-NAME measurements in DM UNX animals. Similarly, L-NAME challenge induced a significant reduction of renal transverse relaxation time (T2*) at MRI in control animals, indicating reduced renal oxygenation after L-NAME injection compared with baseline. DM UNX animals did not show a significant T2* reduction after NO synthesis inhibition in the renal cortex and attenuated T2* reduction in the outer medulla. MRI parameters of tissue diffusion were not affected by L-NAME in all groups. In conclusion, BOLD imaging proved valuable to noninvasively measure renal vascular reactivity upon NO synthesis inhibition in control animals and to detect impaired vascular reactivity in animals with diabetic nephropathy.
authors.affiliation: Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany. hueper.katja@mh-hannover.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Hueper
authors.forename: Dagmar
authors.initials: D
authors.lastname: Hartung
authors.forename: Marcel
authors.initials: M
authors.lastname: Gutberlet
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
authors.forename: Holger
authors.initials: H
authors.lastname: Sann
authors.forename: Bettina
authors.initials: B
authors.lastname: Husen
authors.forename: Frank
authors.initials: F
authors.lastname: Wacker
authors.forename: Dania
authors.initials: D
authors.lastname: Reiche
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000201:enzymology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology* / Q000503:physiopathology; D059305:Diet, High-Fat; D004058:Diffusion; D056324:Diffusion Tensor Imaging; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009392:Nephrectomy; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester
keywords: N-nitro-l-arginine methyle ester; blood oxygen level-dependent imaging; diabetic nephropathy; diffusion tensor imaging; nitric oxide; vascular reactivity