Hirooka Y, Polson J W, Dampney R A
Department of Physiology, University of Sydney, N.S.W., Australia.
J Hypertens. 1996 Nov;14(11):1317-24. doi: 10.1097/00004872-199611000-00010.
It has been shown that nitric oxide (NO) plays an important role in the central control of arterial pressure and sympathetic nerve activity. The aim of this study was to determine whether NO can regulate sympathetic nerve activity by an action on pressor neurons within the rostral part of the ventrolateral medulla (VLM).
Experiments were performed on anaesthetized rabbits with denervated arterial and cardiopulmonary baroreceptors. The mean arterial pressure (MAP), heart rate and renal sympathetic nerve activity were measured. Microinjections of the NO donors sodium nitroprusside (SNP, 4-50 nmol) and S-nitroso-glutathione (10 nmol), the NO precursor L-arginine (50 nmol) and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 50 nmol), were made into the functionally identified pressor region in the rostral VLM. The effects of SNP were also determined before and after injection of 5 nmol methylene blue into the same area. In control experiments, injections of D-arginine (50 nmol) and D-NAME (50 nmol), which are the inactive isomers of L-arginine and L-NAME, respectively, were also made into the functionally identified pressor region in the rostral VLM.
Microinjections of SNP into the rostral VLM pressor region produced a dose-dependent increase in mean arterial pressure and renal sympathetic nerve activity. At the highest dose of 50 nmol, the increase in MAP was 26 +/- 5 mmHg (P < 0.001) and the sympathetic nerve activity was 53 +/- 5% (P < 0.001). These effects were abolished following methylene blue injection into the same region. Injection of 10 nmol S-nitroso-glutathione also produced increases in MAP (15 +/- 2 mmHg, P < 0.001) and in renal sympathetic nerve activity (28 +/- 2%, P < 0.001). Microinjections of L- or D-arginine resulted in very small depressor responses, but had no significant effect on renal sympathetic nerve activity. Microinjections of L-NAME, but not of D-NAME, caused significant decreases in MAP (19 +/- 1 mmHg, P < 0.001) and in sympathetic nerve activity (30 +/- 3%, P < 0.001).
The results indicate that, in the anaesthetized rabbit with denervated baroreceptors, NO has a pressor and sympathoexcitatory action in the rostral VLM, which is mediated by a cyclic GMP-dependent mechanism. Second, endogenous NO may modulate sympathetic activity tonically, by a direct or indirect action on sympathoexcitatory neurons within the rostral VLM.
已表明一氧化氮（NO）在动脉血压和交感神经活动的中枢控制中起重要作用。本研究的目的是确定NO是否可通过作用于延髓腹外侧区（VLM）头端的升压神经元来调节交感神经活动。
在去神经支配的动脉和心肺压力感受器的麻醉兔身上进行实验。测量平均动脉压（MAP）、心率和肾交感神经活动。将NO供体硝普钠（SNP，4 - 50 nmol）和S - 亚硝基谷胱甘肽（10 nmol）、NO前体L - 精氨酸（50 nmol）以及NO合酶抑制剂Nω - 硝基 - L - 精氨酸甲酯（L - NAME，50 nmol）微量注射到VLM头端功能确定的升压区域。在向同一区域注射5 nmol亚甲蓝之前和之后也测定了SNP的作用。在对照实验中，还将L - 精氨酸和L - NAME的无活性异构体D - 精氨酸（50 nmol）和D - NAME（5 nmol）微量注射到VLM头端功能确定的升压区域。
向VLM头端升压区域微量注射SNP导致平均动脉压和肾交感神经活动呈剂量依赖性增加。在最高剂量50 nmol时，MAP升高26±5 mmHg（P < 0.001），交感神经活动升高53±5%（P < 0.001）。向同一区域注射亚甲蓝后这些作用被消除。注射10 nmol S - 亚硝基谷胱甘肽也使MAP升高（15±2 mmHg，P < 0.001）和肾交感神经活动升高（28±2%，P < 0.001）。微量注射L - 或D - 精氨酸导致非常小的降压反应，但对肾交感神经活动无显著影响。微量注射L - NAME而非D - NAME导致MAP显著降低（19±1 mmHg，P < 0.001）和交感神经活动显著降低（30±3%，P < 0.001）。
结果表明，在去神经支配压力感受器的麻醉兔中，NO在VLM头端具有升压和交感兴奋作用，这是由环磷酸鸟苷依赖性机制介导的。其次，内源性NO可能通过对VLM头端交感兴奋神经元的直接或间接作用来持续调节交感活动。
