期刊
JOURNAL OF APPLIED PHYSIOLOGY
卷 95, 期 5, 页码 1767-1774出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00759.2002
关键词
intermittent hypoxia; chronic sustained hypoxia; hypoxic ventilatory response; glutamate receptors; N-methyl-D-aspartate
资金
- NCRR NIH HHS [P20 RR-15576] Funding Source: Medline
- NHLBI NIH HHS [HL-65270, HL-69932, HL-63912] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015576] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL063912, R01HL065270, R01HL069932] Funding Source: NIH RePORTER
The effects of chronic sustained hypoxia (SH) on ventilation have been thoroughly studied. However, the effects of intermittent hypoxia (IH), a more prevalent condition in health and disease are currently unknown. We hypothesized that the ventilatory consequences of SH and IH may differ and be related to changes in N-methyl-D-aspartate (NMDA) glutamate receptor subunit expression. To examine these issues, Sprague-Dawley adult male rats were exposed to 30 days of either SH (10% O-2) or IH (21% and 10% O-2 alternations every 90 s) or to normoxia (RA), at the end of which ventilatory and O-2 consumption responses to a 20-min acute hypoxic challenge (10% O-2) were conducted. In addition, dorsocaudal brain stem tissue lysates were harvested at 1 h, 6 h, 1 day, 3 days, 7 days, 14 days, and 30 days of SH and IH and analyzed for NR1, NR2A, and NR2B NMDA glutamate receptor expression by immunoblotting. Normoxic ventilation was higher after both SH and IH (P < 0.001). Peak hypoxic ventilatory response was higher after SH but not after IH compared with RA. However, hypoxic ventilatory decline was more prominent after SH than IH (P < 0.001). NR1 expression showed a biphasic pattern of expression over time that was essentially identical after IH and SH (P value not significant). However, NR2A and NR2B expression was higher in IH compared with SH and RA (P < 0.01). We conclude that long-lasting exposures to SH and IH enhance normoxic ventilation but are associated with different time domains of ventilation during acute hypoxia that may be accounted in part by changes in NMDA glutamate receptor subunit expression.
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