Liu J L, Murakami H, Zucker I H
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198-4575, USA.
Circ Res. 1998 Mar 9;82(4):496-502. doi: 10.1161/01.res.82.4.496.
Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotensin II (Ang II) increases sympathetic outflow, one factor for this discrepancy may be the difference in the resting level of Ang II, which may be lower in well-trained conscious animals. In the present study, the effects of blockade of NO synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg IV) on resting RSNA with and without a background intravenous infusion of Ang II (10 ng.kg(-1).min(-1)) was investigated in conscious rabbits. Intravenous administration of L-NAME (30 mg/kg) caused an increase in mean arterial blood pressure (MAP, from 80.4+/-2.9 to 92.8+/-2.5; P=.0001) and a decrease in RSNA (from 100+/-0% to 53.4+/-8.6%, P=.0016). When the elevated blood pressure was returned to control by infusion of hydralazine (0.01 to 0.06 mg.kg(-1).min(-1)), RSNA returned to the level before L-NAME administration. During a sustained infusion of Ang II (10 ng.kg(-1).min(-1)), L-NAME increased MAP from 89.2+/-2.9 to 109.0+/-4.3 mm Hg (P=.0101) and decreased RSNA from 100.0+/-0% to 53.7+/-7.5% (P=.0013). Under this circumstance, however, when the MAP was returned to the level that existed before the administration of L-NAME, RSNA increased significantly above the level that existed before the administration of L-NAME (164.5+/-17.7% versus 100+/-0%, P=.0151). The enhancement of the sympathetic response by Ang II was completely blocked by the AT1 receptor antagonist, losartan. In contrast, during a background infusion of phenylephrine, which increased MAP to the same level as produced by Ang II, L-NAME had no effect on RSNA when MAP was returned to the control level. Nomega-Nitro-D-arginine methyl ester had no effect on MAP and RSNA. Intravenous infusion of Ang II alone for 75 minutes had no effect on RSNA when MAP was returned to control levels. These data suggest that an elevated level of Ang II is critical for the inhibitory effect of NO on sympathetic outflow in conscious rabbits and imply that these two substances have a major impact on the regulation of sympathetic outflow.
越来越多的证据表明，内源性一氧化氮（NO）可抑制麻醉动物的交感神经输出。然而，在本实验室最近的一项研究中，我们未能找到任何证据表明清醒家兔在一氧化氮合成被阻断时肾交感神经活动（RSNA）会增加。由于血管紧张素II（Ang II）会增加交感神经输出，造成这种差异的一个因素可能是Ang II的静息水平不同，在训练有素的清醒动物中其水平可能较低。在本研究中，我们研究了用Nω-硝基-L-精氨酸甲酯（L-NAME，30 mg/kg静脉注射）阻断一氧化氮合成对清醒家兔在有或无背景静脉输注Ang II（10 ng·kg⁻¹·min⁻¹）情况下静息RSNA的影响。静脉注射L-NAME（30 mg/kg）导致平均动脉血压（MAP）升高（从80.4±2.9升至92.8±2.5；P = 0.0001），RSNA降低（从100±0%降至53.4±8.6%，P = 0.0016）。当通过输注肼屈嗪（0.01至0.06 mg·kg⁻¹·min⁻¹）使升高的血压恢复到对照水平时，RSNA恢复到L-NAME给药前的水平。在持续输注Ang II（10 ng·kg⁻¹·min⁻¹）期间，L-NAME使MAP从89.2±2.9升至109.0±4.3 mmHg（P = 0.0101），RSNA从100.0±0%降至53.7±7.5%（P = 0.0013）。然而，在这种情况下，当MAP恢复到L-NAME给药前的水平时，RSNA显著高于L-NAME给药前的水平（164.5±17.7%对100±0%，P = 0.0151）。Ang II对交感反应的增强作用被AT1受体拮抗剂氯沙坦完全阻断。相比之下，在背景输注去氧肾上腺素使MAP升高到与Ang II产生的水平相同时，当MAP恢复到对照水平时，L-NAME对RSNA没有影响。Nω-硝基-D-精氨酸甲酯对MAP和RSNA没有影响。当MAP恢复到对照水平时，单独静脉输注Ang II 75分钟对RSNA没有影响。这些数据表明，Ang II水平升高对于NO对清醒家兔交感神经输出的抑制作用至关重要，这意味着这两种物质对交感神经输出的调节有重大影响。
