Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice.

Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice.
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雄性内皮NOS基因敲除小鼠在高碳酸气体刺激期间和之后的通气反应受损,而雌性小鼠则无此现象。

DOI:
10.1038/s41598-021-99922-5
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发表时间:
2021-10-18
期刊:
影响因子:
4.6
通讯作者:
Lewis SJ
Lewis SJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Getsy PM;Sundararajan S;May WJ;von Schill GC;McLaughlin DK;Palmer LA;Lewis SJ

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在自由活动的雌性和雄性野生型(WT)C57 BL 6小鼠和C57 BL 6背景的eNOS敲除(eNOS-/-)小鼠中,使用全身体积描记法评估了内皮型一氧化氮合酶(eNOS)在高碳酸气体攻击(HCC,5%CO2,21%O2,74%N2)期间和之后的解释性反应中的作用。HCC引起了一系列在雄性和雌性WT小鼠中相似的呼吸反应,如呼吸频率增加(吸气和呼气时间福尔斯下降),潮气量、每分钟通气量、吸气和呼气峰流量以及吸气和呼气驱动增加。eNOS-/-雄性小鼠的每分钟通气量、峰值吸气流量和吸气驱动增加较小,吸气时间减少较小。雌性eNOS-/-小鼠的通气反应与雌性WT小鼠相似。雄性和雌性WT小鼠返回室内空气后的兴奋性兴奋相相似。然而,肝癌后呼吸频率增加(吸气时间减少),潮气量、每分钟通气量、吸气驱动力增加(即,潮气量/吸气时间)和呼气驱动(即,潮气量/呼气时间),并且雄性eNOS-/-小鼠的吸气和呼气峰流量小于雄性WT小鼠。相比之下,雌性eNOS-/-小鼠的HCC后反应与雌性WT小鼠相同。这些发现提供了第一个证据,即eNOS的损失影响雄性C57 BL 6小鼠在HCC期间和之后的免疫反应,而雌性C57 BL 6小鼠可以补偿eNOS的损失,至少在触发对HCC的免疫反应方面。
The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.
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