Kakoki M, Zou A P, Mattson D L
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Jul;281(1):R91-7. doi: 10.1152/ajpregu.2001.281.1.R91.
The role of nitric oxide (NO) produced by NO synthase 1 (NOS1) in the renal vasculature remains undetermined. In the present study, we investigated the influence of systemic inhibition of NOS1 by intravenous administration of N(omega)-propyl-L-arginine (L-NPA; 1 mg. kg(-1). h(-1)) and N(5)-(1-imino-3-butenyl)-L-ornithine (v-NIO; 1 mg. kg(-1). h(-1)), highly selective NOS1 inhibitors, on renal cortical and medullary blood flow and interstitial NO concentration in Sprague-Dawley rats. Arterial blood pressure was significantly decreased by administration of both NOS1-selective inhibitors (-11 +/- 1 mmHg with L-NPA and -7 +/- 1 mmHg with v-NIO; n = 9/group). Laser-Doppler flowmetry experiments demonstrated that blood flow in the renal cortex and medulla was not significantly altered following administration of either NOS1-selective inhibitor. In contrast, the renal interstitial level of NO assessed by an in vivo microdialysis oxyhemoglobin-trapping technique was significantly decreased in both the renal cortex (by 36-42%) and medulla (by 32-40%) following administration of L-NPA (n = 8) or v-NIO (n = 8). Subsequent infusion of the nonspecific NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 50 mg. kg(-1). h(-1)) to rats pretreated with either of the NOS1-selective inhibitors significantly increased mean arterial pressure by 38-45 mmHg and significantly decreased cortical (25-29%) and medullary (37-43%) blood flow. In addition, L-NAME further decreased NO in the renal cortex (73-77%) and medulla (62-71%). To determine if a 40% decrease in NO could alter renal blood flow, a lower dose of L-NAME (5 mg. kg(-1). h(-1); n = 8) was administered to a separate group of rats. The low dose of L-NAME reduced interstitial NO (cortex 39%, medulla 38%) and significantly decreased blood flow (cortex 23-24%, medulla 31-33%). These results suggest that NOS1 does not regulate basal blood flow in the renal cortex or medulla, despite the observation that a considerable portion of NO in the renal interstitial space appears to be produced by NOS1.
一氧化氮合酶1（NOS1）产生的一氧化氮（NO）在肾血管系统中的作用尚未明确。在本研究中，我们通过静脉注射N（ω）-丙基-L-精氨酸（L-NPA；1 mg·kg⁻¹·h⁻¹）和N⁵-（1-亚氨基-3-丁烯基）-L-鸟氨酸（v-NIO；1 mg·kg⁻¹·h⁻¹）这两种高选择性NOS1抑制剂，研究了全身抑制NOS1对Sprague-Dawley大鼠肾皮质和髓质血流以及间质NO浓度的影响。两种NOS1选择性抑制剂给药后动脉血压均显著降低（L-NPA组降低-11±1 mmHg，v-NIO组降低-7±1 mmHg；每组n = 9）。激光多普勒血流仪实验表明，给予任何一种NOS1选择性抑制剂后，肾皮质和髓质的血流均无显著改变。相反，采用体内微透析氧合血红蛋白捕获技术评估的肾间质NO水平，在给予L-NPA（n = 8）或v-NIO（n = 8）后，肾皮质（降低36 - 42%）和髓质（降低32 - 40%）均显著下降。随后向预先用任何一种NOS1选择性抑制剂处理过 的大鼠输注非特异性NOS抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME；50 mg·kg⁻¹·h⁻¹），平均动脉压显著升高38 - 45 mmHg，皮质（降低25 - 29%）和髓质（降低37 - 43%）血流显著减少。此外，L-NAME进一步降低了肾皮质（降低73 - 77%）和髓质（降低62 - 71%）中的NO。为了确定NO降低40%是否会改变肾血流，对另一组大鼠给予较低剂量的L-NAME（5 mg·kg⁻¹·h⁻¹；n = 8）。低剂量的L-NAME降低了间质NO（皮质降低了39%，髓质降低了38%），并显著降低了血流（皮质降低23 - 24%，髓质降低31 - 33%）。这些结果表明，尽管观察到肾间质空间中相当一部分NO似乎是由NOS1产生的，但NOS1并不调节肾皮质或髓质中的基础血流。
