el Karib A O, Sheng J, Betz A L, Malvin R L
Department of Physiology, University of Michigan School of Medicine, Ann Arbor 48109.
Clin Exp Hypertens. 1993 Sep;15(5):819-32. doi: 10.3109/10641969309041644.
An endothelium-derived relaxing factor has been identified as nitric oxide (NO). Peripheral and central administration of nitric oxide synthase inhibitors result in an increase in renal sympathetic nerve activity and an increase in blood pressure. The goal of our study was to determine if the increase in blood pressure following central NO synthase inhibition with N omega-nitro-L-arginine (L-NNA) is caused by the release of renin. Six groups of Sprague-Dawley rats were used. Group I (control) received intracerebroventricular (i.c.v.) artificial cerebrospinal fluid. Groups II & III received i.c.v. L-NNA, 5 & 15 micrograms/min. respectively. Group IV was treated with intravenous L-NNA, 15 micrograms/min. Group V, after bilateral nephrectomy, received i.c.v. L-NNA, 15 micrograms/min. Group VI received i.c.v. L-arginine, 60 micrograms/min. and i.c.v. L-NNA, 15 micrograms/min., simultaneously. Plasma renin concentration was measured in groups I, III, IV & V. Mean arterial blood pressure was significantly increased in groups II, III & V, i.e., following i.c.v. infusion of L-NNA. The increase in mean arterial blood pressure was significantly greater when the dose was increased from 5 to 15 micrograms/min. and it was eliminated when L-arginine was added to the infusion. The increase in blood pressure was attended by no change in heart rate. While the plasma renin concentration increased significantly in group III, this could not explain the increase in blood pressure since the nephrectomized group (V) showed no increase in renin concentration but an equivalent increase in blood pressure. The results show that acute central administration of a low dose of L-NNA increases blood pressure in rats and this increase can be prevented by central administration of L-arginine. However, intravenous infusion of the same dose (15 micrograms/min.) of L-NNA does not change blood pressure. We conclude that L-NNA acts directly within the central nervous system to increase blood pressure by a renin-independent mechanism. These results imply that central nitric oxide plays an important role in the regulation of blood pressure.
一种内皮源性舒张因子已被确认为一氧化氮（NO）。外周和中枢给予一氧化氮合酶抑制剂会导致肾交感神经活动增加以及血压升高。我们研究的目的是确定用Nω-硝基-L-精氨酸（L-NNA）中枢抑制一氧化氮合酶后血压升高是否由肾素释放引起。使用了六组Sprague-Dawley大鼠。第一组（对照组）接受脑室内（i.c.v.）人工脑脊液。第二组和第三组分别接受i.c.v. L-NNA，速率为5和15微克/分钟。第四组用静脉注射L-NNA，速率为15微克/分钟进行治疗。第五组在双侧肾切除术后，接受i.c.v. L-NNA，速率为15微克/分钟。第六组同时接受i.c.v. L-精氨酸，速率为60微克/分钟和i.c.v. L-NNA，速率为15微克/分钟。在第一组、第三组、第四组和第五组中测量血浆肾素浓度。第二组、第三组和第五组，即i.c.v.输注L-NNA后，平均动脉血压显著升高。当剂量从5微克/分钟增加到15微克/分钟时，平均动脉血压的升高显著更大，并且当向输注中添加L-精氨酸时升高被消除。血压升高时心率没有变化。虽然第三组血浆肾素浓度显著增加，但这不能解释血压升高，因为肾切除组（第五组）肾素浓度没有增加但血压有同等程度的升高。结果表明，急性中枢给予低剂量L-NNA会使大鼠血压升高，而中枢给予L-精氨酸可预防这种升高。然而，静脉输注相同剂量（15微克/分钟）的L-NNA不会改变血压。我们得出结论，L-NNA通过一种不依赖肾素的机制直接在中枢神经系统内起作用以升高血压。这些结果表明中枢一氧化氮在血压调节中起重要作用。
