Reactive oxygen species stimulate central and peripheral sympathetic nervous system activity

被引:156
作者
Campese, VM [1 ]
Ye, SH [1 ]
Zhong, HQ [1 ]
Yanamadala, V [1 ]
Ye, Z [1 ]
Chiu, J [1 ]
机构
[1] Univ So Calif, Keck Sch Med, Div Nephrol, Dept Med, Los Angeles, CA 90033 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2004年 / 287卷 / 02期
关键词
hypertension; sympathetic nerve activity; renal nerve activity; nitric oxide synthase; interleukin; 1; beta; N-omega-nitro-L-arginine methyl ester; nitric oxide;
D O I
10.1152/ajpheart.00619.2003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies have implicated reactive oxygen species (ROS) in the pathogenesis of hypertension and activation of the sympathetic nervous system (SNS). Because nitric oxide (NO) exerts a tonic inhibition of central SNS activity, increased production of ROS could enhance inactivation of NO and result in activation of the SNS. To test the hypothesis that ROS may modulate SNS activity, we infused Tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), a superoxide dismutase mimetic, or vehicle either intravenously (250 mug.kg(-1).min(-1)) or in the lateral ventricle (50 mug.kg body wt(-1).min(-1)), and we determined the effects on blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamus (PH) measured by the microdialysis technique, renal sympathetic nerve activity (RSNA) measured by direct microneurography, the abundance of neuronal NO synthase (nNOS)-mRNA in the PH, paraventricular nuclei (PVN), and locus coeruleus (LC) measured by RT-PCR, and the secretion of nitrate/nitrite (NOx) in the dialysate collected front the PH of Sprague-Dawley rats. Tempol reduced BP whether infused intravenously or intracerebroventricularly. Tempol reduced NE secretion front the PH and RSNA when infused intracerebroventricularly but raised NE secretion from the PH and RSNA when infused intravenously. The effects of intravenous Tempol on SNS activity were blunted or abolished by sinoaortic denervation. Tempol increased the abundance of nNOS in the PH, PVN, and LC when infused intracerebroventricularly, but it decreased the abundance of nNOS when infused intravenously. When given intracerebroventricularly, Tempol also reduced the concentration of NOx in the dialysate collected from the PH. Pretreatment with N-omega-nitro-L-arginine methyl ester did not abolish the effects of intracerebral Tempol on BP. heart rate. NE secretion from the PH, and RSNA suggesting that the effects of Tempol on SNS activity may be in part dependent and in part independent of NO. In all, these Studies Support the notion that ROS may raise BP via activation of the SNS. This activation may be mediated in part by downregulation of nNOS and NO production, in part by mechanisms independent of NO. The discrepancy in results between intracerebroventricular and intravenous infusion of Tempol can be best explained by direct inhibitory actions on SNS activity when given intracerebral. By contrast, Ternpol may exert direct vasodilation of the peripheral circulation and reflex activation of the SNS when given intravenously.
引用
收藏
页码:H695 / H703
页数:9
相关论文
共 64 条
  • [1] Nitric oxide depolarizes type II paraventricular nucleus neurons in vitro
    Bains, JS
    Ferguson, AV
    [J]. NEUROSCIENCE, 1997, 79 (01) : 149 - 159
  • [2] Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells
    Ballinger, SW
    Patterson, C
    Yan, CN
    Doan, R
    Burow, DL
    Young, CG
    Yakes, FM
    Van Houten, B
    Ballinger, CA
    Freeman, BA
    Runge, MS
    [J]. CIRCULATION RESEARCH, 2000, 86 (09) : 960 - 966
  • [3] Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response
    Beswick, RA
    Zhang, HF
    Marable, D
    Catravas, JD
    Hill, WD
    Webb, RC
    [J]. HYPERTENSION, 2001, 37 (02) : 781 - 786
  • [4] The dominant role of exogenous or endogenous interleukin-1 beta on expression and activity of inducible nitric oxide synthase in rat microvascular brain endothelial cells
    Bonmann, E
    Suschek, C
    Spranger, M
    KolbBachofen, V
    [J]. NEUROSCIENCE LETTERS, 1997, 230 (02) : 109 - 112
  • [5] LOCALIZATION OF NITRIC-OXIDE SYNTHASE INDICATING A NEURAL ROLE FOR NITRIC-OXIDE
    BREDT, DS
    HWANG, PM
    SNYDER, SH
    [J]. NATURE, 1990, 347 (6295) : 768 - 770
  • [6] CLONED AND EXPRESSED NITRIC-OXIDE SYNTHASE STRUCTURALLY RESEMBLES CYTOCHROME-P-450 REDUCTASE
    BREDT, DS
    HWANG, PM
    GLATT, CE
    LOWENSTEIN, C
    REED, RR
    SNYDER, SH
    [J]. NATURE, 1991, 351 (6329) : 714 - 718
  • [7] IMMEDIATE HYPOTENSIVE AFTEREFFECTS OF POSTERIOR HYPOTHALAMIC-LESIONS IN AWAKE RATS WITH SPONTANEOUS, RENAL, OR DOCA HYPERTENSION
    BUNAG, RD
    EFERAKEYA, AE
    [J]. CARDIOVASCULAR RESEARCH, 1976, 10 (06) : 663 - 671
  • [8] Downregulation of neuronal nitric oxide synthase and interleukin-1β mediates angiotensin II-dependent stimulation of sympathetic nerve activity
    Campese, VM
    Ye, SH
    Zhong, HQ
    [J]. HYPERTENSION, 2002, 39 (02) : 519 - 524
  • [9] BRAIN-STEM AND BULBOSPINAL NEUROTRANSMITTER SYSTEMS IN THE CONTROL OF BLOOD-PRESSURE
    CHALMERS, J
    PILOWSKY, P
    [J]. JOURNAL OF HYPERTENSION, 1991, 9 (08) : 675 - 694
  • [10] BRAIN AMINES AND MODELS OF EXPERIMENTAL HYPERTENSION
    CHALMERS, JP
    [J]. CIRCULATION RESEARCH, 1975, 36 (04) : 469 - 480