The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia.

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

The role of NMDA glutamate receptors in lung injury caused by chronic long-term intermittent hypobaric hypoxia

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

Effects of intravenous and intracerebroventricular theophylline on hypoxic ventilatory depression in anesthetized cats.

OBJECTIVE: The present study was undertaken to investigate the ventilatory response due to sustained isocapnic moderate hypoxia and the possible role of adenosine in hypoxic depression in anesthetized cats. MATERIALS AND METHODS: Cats anesthetized with pentothal sodium (30 mg kg(-1) i.p.) were divided into two groups: treated (n = 11) and control (n = 15). Respiratory frequency (f), tidal volume (VT), minute volume (VE) and systemic arterial blood pressure were recorded during air and 20 min of breathing hypoxic gas mixture (14% O2-86% N2). Isocapnia was maintained by adding fractions of 1% CO2 to the inspired hypoxic gas mixture. The PaO2 and PaCO2 were determined. RESULTS: On hypoxic gas mixture breathing, VT and VE values of the control animals increased significantly, at 5 min to 50 +/- 6 and 53 +/- 6%, respectively, above the prehypoxic air phase value (p < 0.001). After that, the magnitude of increase in VT and VE declined gradually. At 20 min of hypoxia, VT and VE were less than those in prehypoxic air phase (17 +/- 7, 16 +/- 7%, respectively). In cats injected with an adenosine antagonist (theophylline 13.6 mg kg(-1) i.v.), f, VT and VE increased significantly at 5 min of hypoxia (p < 0.001). At 20 min of hypoxia, f, VT and VE were 8 +/- 2, 30 +/- 8, and 39 +/- 8%, respectively, higher than corresponding values of the prehypoxic stage. In cats injected with theophylline (0.5 mg kg(-1)) by cisternal puncture VT and VE increased significantly at 5 min of hypoxia. At 20 min of hypoxia, VT and VE were 27 +/- 7 and 31 +/- 8% higher than those in the prehypoxic air phase. CONCLUSION: The results of this study show that accumulation of adenosine in the brain during hypoxia seems to reduce the response of the central mechanisms to chemoreceptor impulses.