Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia

Attenuation of the hypoxic ventilatory response in adult rats following one month of perinatal hyperoxia
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DOI:
10.1113/jphysiol.1996.sp021616
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发表时间:
1996-09-01
影响因子:
5.5
通讯作者:
Mitchell, GS
Mitchell, GS
中科院分区:
医学1区
文献类型:
--
作者:
Ling, LM;Olson, EB;Mitchell, GS

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1.本研究旨在验证围产期抑制外周动脉化学感受器输入可减弱成年大鼠低氧呼吸反应的假说。围产期外周化学感受器活性的抑制是通过使大鼠在生命的第一个月内暴露于高氧环境中实现的。妊娠晚期的大鼠被安置在60%的氧气环境中,从出生前几天开始将幼鼠暴露在高氧环境中,直到出生后第28天回到正常氧状态。这些围产期处理的大鼠随后在常氧条件下饲养到成年(3-5个月大)。除了母鼠,成年-雄性大鼠也暴露在高氧环境中,形成了一个成人处理的对照组。高氧暴露2至4个月后,将处理后的大鼠与年龄相近的未处理的雄性大鼠进行比较。采用全身流通式体积描记仪测定未麻醉成年大鼠的低氧和高二氧化碳呼吸反应。在中度缺氧(动脉血氧分压,P-a、P-O2与48毫米汞柱相近)条件下,围产期处理组大鼠的V-E(分钟通气量)和V-E/V-CO2(通气量与CO2产生量之比)分别增加16.7+/-4.0和35.4+/-3.4%,而对照组增加更多(51.4+/-2.8和83.1+/-4.3%;P<10(-6))。与低氧呼吸反应受损相反,未处理的对照组和围产期处理的大鼠对高碳酸血症(5%CO2)的呼吸反应相似。缺氧反应受损是围产期处理的大鼠所特有的,因为在成年处理的大鼠中,缺氧的呼吸反应没有减弱。结果表明,在出生后第一个月经历过高氧的成年大鼠,对低氧血症的呼吸反应显著减弱,这表明正常的低氧呼吸控制机制容易受到发育可塑性的影响。
1. This study was designed to test the hypothesis that perinatal suppression of peripheral arterial chemoreceptor inputs attenuates the hypoxic ventilatory response in adult rats. Perinatal suppression of peripheral chemoreceptor activity was achieved by exposing rats to hyperoxia throughout the first month of life.2. Late gestation pregnant rats were housed in a 60% O-2 environment, exposing the pups to hyperoxia from several days prior to birth until they were returned to normoxia on postnatal day 28. These perinatally treated rats were then reared to adulthood (3-5 months old) in normoxia. In addition to the mother rats, adult-male rats were also exposed to hyperoxia, creating an adult-treated control group. Two to four months after the hyperoxic exposure, treated rats were compared with untreated male rats of similar age.3. A whole-body, flow-through plethysmograph was used to measure hyrpoxic and hypercapnic ventilatory responses of the unanaesthetized adult rats. In moderate hypoxia (arterial oxygen partial pressure, P-a,P-O2 similar to 48 mmHg), V-E (minute ventilation) and the ratio V-E/V-CO2 (ventilation relative to CO2 production) increased by 16.7 +/- 4.0 and 35.4 +/- 3.4%, respectively, in perinatal-treated rats (means +/- S.E.M), but increased more in untreated control rats (51.4 +/- 2.8 and 83.1 +/- 4.3%; both P < 10(-6)).4. In contrast to the impaired hypoxic ventilatory response, ventilatory responses to hypercapnia (5% CO2) were similar between untreated control and perinatal-treated rats.5. Impaired hypoxic responsiveness was unique to the perinatal-treated rats since hypoxic ventilatory responses were not attenuated in adult-treated rats.6. The results indicate that ventilatory responses to hypoxaemia are greatly attenuated in adult rats that had experienced hyperoxia during their first month of life, and suggest that normal hypoxic ventilatory control mechanisms are susceptible to developmental plasticity.