Schwenke D O, Pearson J T, Kangawa K, Shirai M
Department of Biochemistry, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Acta Physiol (Oxf). 2006 Apr;186(4):309-18. doi: 10.1111/j.1748-1716.2006.01570.x.
Hypoxia initiates an increase in ventilation (VE) through a cascade of events of which central nitric oxide (NO) has been implicated as an important neuromodulator. There have not been any reports describing the consequences of long-term imbalances in the central NO pathways on the modulation of the acute hypoxic ventilatory response (HVR). Chronic hypoxia (CH) can potentially modify the HVR, and so we hypothesized that central NO may be involved. In this study we describe the long-term role of central NO in the modulation of HVR before and after CH.
Male Sprague-Dawley rats (BW c. 200-320 g; n = 21) were implanted with an osmotic pump for continuous intracerebroventricular administration of either artificial cerebrospinal fluid (control), Nomega-nitro-L-arginine methyl ester (L-NAME) (150 microg kg(-1) day(-1)) or the NO-donor, 3-[4-morpholinyl]-sydnonimine-hydrochloride (SIN-1) (100 microg kg(-1) day(-1)). The VE response to acute poikilocapnic hypoxia (8% O2 for 20 min) was measured by plethysmography seven days after surgery, in normoxia, and again after 14 days of exposure to CH (CH = 12% O2).
The magnitude of the HVR (c. 230% increase in VE) was unaltered by centrally infusing either L-NAME or SIN-1 for 1 week. CH did not modify the HVR, although baseline VE and HVR were shifted downward by L-NAME during CH - because of a reduction in the frequency component.
These results suggest that long-term alterations in central NO levels may not alter the HVR under moderate CH, presumably because of the onset/development of compensatory mechanisms. However, NO appears to be an important component of the HVR following CH.
缺氧通过一系列事件引发通气量（VE）增加，其中中枢一氧化氮（NO）被认为是一种重要的神经调节剂。目前尚无关于中枢NO通路长期失衡对急性缺氧通气反应（HVR）调节影响的报道。慢性缺氧（CH）可能会改变HVR，因此我们推测中枢NO可能参与其中。在本研究中，我们描述了中枢NO在CH前后对HVR调节的长期作用。
雄性Sprague-Dawley大鼠（体重约200 - 320 g；n = 21）植入渗透泵，用于持续脑室内注射人工脑脊液（对照组）、N-硝基-L-精氨酸甲酯（L-NAME）（150 μg·kg⁻¹·天⁻¹）或NO供体3-[4-吗啉基]-西多胺盐酸盐（SIN-1）（100 μg·kg⁻¹·天⁻¹）。术后7天，在常氧条件下，通过体积描记法测量对急性变温性低氧（8% O₂，持续20分钟）的VE反应，在暴露于CH（CH = 12% O₂）14天后再次测量。
中枢注射L-NAME或SIN-1 1周后，HVR的幅度（VE增加约230%）未改变。CH并未改变HVR，尽管在CH期间L-NAME使基线VE和HVR向下偏移 - 这是由于频率成分降低。
这些结果表明，在中度CH条件下，中枢NO水平的长期改变可能不会改变HVR，推测是由于代偿机制的启动/发展。然而，NO似乎是CH后HVR的重要组成部分。
