Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany.
Am J Physiol Renal Physiol. 2013 Nov 15;305(10):F1428-35. doi: 10.1152/ajprenal.00123.2013. Epub 2013 Sep 4.
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.
糖尿病与血管反应性受损和糖尿病肾病的发生有关。在链脲佐菌素诱导的糖尿病肾病大鼠模型中，通过非侵入性磁共振扩散张量成像和血氧水平依赖性（BOLD）成像分别确定全身一氧化氮（NO）合成抑制对肾内扩散和氧合的影响。糖尿病诱导 8 周后，21 只大鼠 [每组 n = 7 只，未治疗对照组、糖尿病组和单侧肾切除糖尿病组（DM UNX 组）] 接受 MRI 检查。在使用 N-硝基-L-精氨酸甲酯（L-NAME）抑制 NO 合成前后采集扩散张量成像和 BOLD 序列。在相同的大鼠中，在有无 L-NAME 影响的情况下测定平均动脉压和血管传导率。在对照动物中，NO 合成抑制与平均动脉压显著升高 33.8 ± 4.3 mmHg（P < 0.001）和血管传导率显著降低 -17.8 ± 2.0 μl·min(-1)·100 mmHg(-1)（P < 0.001）相关。这些变化在 DM 和 DM UNX 组中均减弱，在 DM UNX 动物中，L-NAME 测量前后无明显差异。同样，L-NAME 挑战在对照动物的 MRI 中引起肾横向弛豫时间（T2*）的显著降低，表明与基线相比，L-NAME 注射后肾氧合减少。在糖尿病肾病动物中，NO 合成抑制后肾皮质 T2* 无明显降低，外髓 T2* 降低减弱。所有组的组织扩散 MRI 参数均不受 L-NAME 影响。总之，BOLD 成像在对照动物中证明在抑制 NO 合成时对测量肾血管反应性具有价值，并在糖尿病肾病动物中检测到血管反应性受损。
