Wiemann Martin, Frede Stilla, Bingmann Dieter, Kiwull Peter, Kiwull-Schöne Heidrun
Department of Physiology, University of Duisburg-Essen, 45122 Essen, Germany.
Am J Respir Crit Care Med. 2005 Jul 15;172(2):244-9. doi: 10.1164/rccm.200411-1567OC. Epub 2005 Jun 9.
In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in chemosensitive neurons of the ventrolateral brainstem augments central respiratory drive in anesthetized rabbits.
To further explore the possible role of this exchanger for the control of breathing, we examined the individual relationship between brainstem NHE3 abundance and ventilation in rabbits during wakefulness.
In 32 adult male rabbits on standard nutritional alkali load, alveolar ventilation, metabolic CO2 production, and blood gases were determined, together with arterial and urinary acid-base status and renal base control functions. Expression of NHE3 in brainstem tissue from the obex region was determined by quantitative real-time reverse-transcription polymerase chain reaction analysis.
Regarding the distribution above and below the median, we classified high and low brainstem NHE3 animals, expressing a mean (+/- SEM) NHE3 mRNA of 2.08 +/- 0.28 and 0.72 +/- 0.06 fg cDNA/mg RNA, respectively. Alveolar ventilation of high brainstem NHE3 animals was lower than that of low brainstem NHE3 animals (715 +/- 36 vs. 919 +/- 41 ml . minute(-1); p < 0.01), a finding also reflected by a marked difference in Pa(CO2) (5.24 +/- 0.16 vs. 4.44 +/- 0.15 kPa; p < 0.01). Among possible secondary factors, CO2 production, systemic base excess, and fractional renal base reabsorption were not found to be different.
We conclude that the level of brainstem NHE3 expression-most likely via intracellular pH modulation-contributes to the individual control of breathing and Pa(CO2) in conscious rabbits by adjusting the set point and the loop gain of the system.
在麻醉兔中，抑制延髓腹外侧化学感受性神经元中的钠/质子交换体3（NHE3）可增强中枢呼吸驱动。
为进一步探究该交换体在呼吸控制中的可能作用，我们研究了清醒兔脑干NHE3丰度与通气之间的个体关系。
对32只接受标准营养性碱负荷的成年雄性兔，测定其肺泡通气、代谢性二氧化碳产生量、血气，以及动脉和尿液酸碱状态及肾脏碱控制功能。通过定量实时逆转录聚合酶链反应分析确定延髓后区脑干组织中NHE3的表达。
根据中位数上下的分布，我们将脑干NHE3高表达和低表达的动物分类，其NHE3 mRNA平均（±标准误）分别为2.08±0.28和0.72±0.06 fg cDNA/mg RNA。脑干NHE3高表达动物的肺泡通气低于脑干NHE3低表达动物（715±36 vs. 919±41 ml·分钟⁻¹；p<0.01），这一结果也反映在动脉血二氧化碳分压（Pa(CO2)）的显著差异上（5.24±0.16 vs. 4.44±0.15 kPa；p<0.01）。在可能的次要因素中，未发现二氧化碳产生量、全身碱剩余和肾脏碱重吸收分数有差异。
我们得出结论，脑干NHE3的表达水平——很可能通过细胞内pH调节——通过调整系统的设定点和回路增益，对清醒兔的呼吸和Pa(CO2)的个体控制起作用。
