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Aim To investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on relaxation of thoracic aorta rings in male developing rats and the underlying mechanisms. Methods Male neonatal Spra-gue-Dawlay ( SD) rats were randomly divided into eight groups respectively: CIHH treatment group (CIHH), group of one-week post-CIHH (CIHH-pl), group of two-week post-CIHH ( CIHH-p2 ) , group of three-week post-CIHH (CIHH-p3 ) , control group for CIHH (Con), control group for CIHH-pl (Con-1), control group for CIHH-p2 ( Con-2) and control group for CIHH-p3 (Con-3 ). Rats in CIHH groups were put into a hypobaric chamber with the mother rats 1 ~ 3 days before the birth to get a hypobaric hypoxia exposure mimicking 3 km altitude for 42 days, 5 hours daily. Rats in control groups were kept in the same environment as CIHH rats except hypoxia exposure. After anaesthetized with pentobarbital sodium (50 mg • kg-1 i. p. ), the thorax of rats was opened and thoracic aorta rings were made. The artery rings were placed in the bath chamber filled with K-H solution, and the relaxation of artery rings was recorded under normoxia or a-cute hypoxia conditions, respectively. Results (1) Under normoxia condition, the acetylcholine ( ACh)-induced relaxation of thoracic aorta increased obviously in CIHH groups compared with corresponding Con groups ( P < 0. 05 ). ( 2 ) The enhancing effect of CIHH treatment on thoracic aorta could be maintained for at least three weeks (P < 0. 05). (3 ) Under acute hypoxia condition, ACh-induced relaxation of thoracic aorta in each group decreased obviously, but the decrease in CIHH groups was significant less than that in Con groups ( P < 0.05 ). (4) The enhancement of CIHH on relaxation of thoracic aorta could be reversed by indomethacin (Indo), a cyclooxygenase inhibitor, glibenclamide (Gli), a KATP blocker, and Tempo, a free radical scavenger. Conclusions CIHH augments endothelium-dependent relaxation in thoracic aorta of developing rats. Also, CIHH can antagonize the inhibition of acute hypoxia on relaxation of thoracic aorta. The enhancing effect of CIHH treatment may be related with the increase of prostacyclin, the opening of KATP and free radical production.
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Newborn calves are still often registered to have dyspepsia or acute hypoxia. These disturbances are very often accompanied by the development of hemostasiopathy. There are no definite approaches to its correction yet. Aim: To determine activity dynamics of coagulation hemostasis in newborn calves with dyspepsia or after acute hypoxia at birth against the background of cresacin and hamavit application. Materials and Methods: We examined 33 newborn calves after acute hypoxia at birth (experimental group №1) and 38 calves with noninfectious dyspepsia (experimental group №2). In the course of 5 days all the experimental calves were given cresacin 4mg/kg a day in the morning for drinking and were injected hamavit intramuscularly 0.03 mg/kg once a day in the morning. We applied biochemical, hemostatic and statistical methods of investigation. The control group in our research was composed of 35 healthy newborn calves. Results of Research: Both groups of experimental calves were noted to have similar level rise of plasma lipids’ peroxidation, strengthening of coagulation process, weakening of anticoagulation processes and fibrinolysis. Application of cresacin and hamavit combination to the examined animals provided similar positive dynamics of all the accountable indices in them. In the result of their application we noted some lowering of plasma acylhydroperoxides’ level (more than in 2.2 times) on behalf of the increase of its antioxidant activity (more than by 30.0%) till the level of the norm. The newborn calves with dyspepsia or after acute hypoxia turned out to be able to reach full activity normalization of all the initially activated coagulation factors against the background of the conducted correction. The time of registered coagulation tests in the observed newborn calves from both experimental groups reached the level of the control values against the background of the correction. In the result of the conducted correction the activity of antithrombin III and protein C in the observed calves from the experimental groups increased by more than 13.0% and by more than 15.0% what provided their normalization. It was accompanied by level rise of plasminogen what provided activity normalization of fibrinolysis system in all the experimental animals. Conclusion: Newborn calves with dyspepsia or after acute hypoxia at birth are characterized by coagulation activity and weakening of plasma anticoagulant and fibrinolytic mechanisms. The application of cresacin and hamavit combination to both categories of newborn calves provides normalization of plasma coagulation activity and mechanisms of its limitation.
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OBJECTIVE: To study the preventing effects of p-coumaric acid(p-CA) on acute hypoxia-induced pulmonary edema by mice experiments. METHODS: Acute-hypoxia model was established using a normobaric hypoxia chamber in vivo. Salidroside was set as a positive control drug. And the test period was 7 d using a method of intragastric administration. The measurements including pulmonary water content, HE staining, inflammatory factors, anti-oxidative indexes and Na+, K+-ATPase were performed to determine the efficacies and mechanisms of p-CA on preventive against acute hypoxia-induced pulmonary edema. RESULTS: As compared with the normal group, pulmonary water contents increased significantly by 3.56% in the mice treated with acute hypoxia (9.5% O2) for 6 h (control group) (P<0.01), and administration with p-CA (25, 100 mg•kg-1•d-1) for 7 d could significantly reduce this index (P<0.05), which was as effective as the positive group. The action mechanisms of p-CA could be due to its abilities of improving the activity of Na+, K+-ATPase, enhancing antioxidant capacity (SOD↑, CAT↑ and MDA↓) and inhibiting inflammatory factors (IL-1β and IL-6). CONCLUSION: p-CA has greater preventive effects on acute hypoxia-induced pulmonary edema in mice.
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The relationship between PEPT1 (peptide transporter) and drug efficacy has drawn more and more attention in the treatment of disease. PEPT1 represents a promising strategy for improvement of drug bioavailability and an important starting point for clinical rationalization of drug selection. The effect of PEPT1 on transport and pharmacokinetics of amoxicillin was investigated under hypoxia condition at high altitude in rat. The mRNA and protein expressions of PEPT1 were increased by 36.87%, 216.21%, 577.8% and 535.9% respectively in the hypoxia group in the small intestine and kidney of rats. However, the mRNA and protein expressions of PEPT1 were reduced by 43.90% and 84.7% in the liver. Compared with the control group, the AUC, tmax, Cmax, MRT and t1/2 of amoxicillin were significantly enhanced by 312.17%, 63.04%, 110.93%, 67.11% and 16.96% respectively in the hypoxia group, while the CL was significantly decreased by 74.51%. After acute exposure to high altitude, the expressions of drug transporter PEPT1 were distinctly changed in rat tissues, which can affect the pharmacokinetics of amoxicillin.
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The drug transporter play a key role in the absorption of drugs. Investigation of the changes of drug transporters in response to hypoxia will provide insight into the mechanism of drug absorption. In this study we investigated the mRNA and protein expression of the transporter P-gp after acute hypoxia, and evaluated the effects of P-gp changes on absorption of levofloxacin in the intestine. The relative expression of mRNA and protein were reduced by 50.80% and 71.30% (PP<0.05). These results suggest that hypoxia may decrease the expression of P-gp in the intestine to reduce the excretion of levofloxacin and increase the absorption.
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Objective: To study the effect and the mechanism of acute hypoxia on Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA) induced intracellular calcium cation enhancement in rat distal pulmonary venous smooth muscle cells (PVSMC) . Methods: The PVSMC were isolated from 6 male SD rats and the cells were cultured for further experiment. Enhancing effects of CPA, acute hypoxia (4% O2) on [Ca2+]i in distal PVSMC and the interventional effects of 2 store-operated Ca2+ channels (SOCC) inhibitors, NiCl2 and SKF96365 on [Ca2+]i in distal PVSMC were tested by lfuorescence microscope and intracellular [Ca2+] examining system. Results: When PVSMC were perfused with Ca2+-free Krebs solution containing 5 μmol/L nifedipine, 10 μmol/L CPA caused a slight elevation of [Ca2+]i, and acute hypoxia obviously enhanced the [Ca2+]i in PVSMC. When restoration of extracellular [Ca2+] to 2.5 mmol/L, 10 μmol/L CPA caused signiifcant elevation of [Ca2+]i, and acute hypoxia obviously enhanced [Ca2+]i induced by CPA in PVSMC. The SOCC inhibitors, NiCl2 (500 μmol/L) and SKF96365 (50 μmol/L) distinctively attenuated the elevation of [Ca2+]i by hypoxia and CPA. However, NiCl2 and SKF96365 had no effect on high potassium (60 mmol/L KCl Krebs solution) induced elevation of [Ca2+]i in distal PVSMC. Conclusion: Acute hypoxia enhanced the elevation of [Ca2+]i induced by CPA; such effect could be selectively blocked by SOCC inhibitor which indicated that acute hypoxia could enhance the activity of SOCC in rat distal PVSMC.
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Objective To explore the efficacy of low tidal volume ventilation strategy in children with acute hypoxia respiratory failure (AHRF).Methods A total of 79 hospitalized children with AHRF from Aug 2006 to Jul 2011 in PICU of Kunming Children's Hospital were enrolled in this study.The observation group in-cluded 55 children who received low tidal volume ventilation strategy (6-8 ml /kg),while the other 24 children (control group)were given traditional mechanical ventilation (10-12 ml /kg).Oxygenation situations such as PaO2 ,PaCO2 ,PaO2 /FiO2 ,oxygen index and blood gas pH value,organ function,mechanical ventilation complica-tions,hospitalization days and expenses in PICU and the mortality were observed.Results (1)PaO2 ,PaO2 /FiO2 and oxygen index in the observation group were better than those in control group after 24 h mechanical ventilation [(68.51 ±7.53)mmHg(1 mmHg =0.133 kPa)vs.(61.64 ±9.28)mmHg,(162.9 ±21.84)mmHg vs.(152.1 ± 19.03)mmHg,and 18.85 ±4.1 vs.26.53 ±5.2,respectively],and there were significant differences between two groups (P ﹤0.05);and there were also significant differences between two groups in the results after 48 h and 72 h mechanical ventilation.(2)The PaCO2 was (47.48 ±10.52)mmHg after 24 h in observation group,while the PaCO2 in control group was (30.17 ±6.59)mmHg,and it suggested excessive ventilation.(3)Mechanical venti-lation time (7.6 ±3.1)d and hospitalization days (12.8 ±3.6)d were shorter in observation group(P ﹤0.01). Barotrauma (7.3%)and mortality (20.0%)in observation group was significantly lower than those in control group (29.2%,41.6%;P ﹤0.01).The number of damaged organs in observation group was lower than that in control group (P ﹤0.05).Conclusion Low tidal volume ventilation with appropriate positive end expiratory pressure could improve oxygenation,prevent alveolar collapse,reduce complications and mortality for children with AHRF,it should be applied for the treatment of children with AHRF.
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Objective: To investigate the effect of crocin-1 on behavior of learning and memory in rats under acute hypoxia and on the expression of silent information regulator l (SIRT1) in hippocampus of rats. Methods: SD rats were randomly divided into five groups: control, hypoxia model, low-, mid-, and high-dose (25, 50, and 100 mg/kg) crocin-1 groups. The SD rats in crocin-1 groups were im administered once daily for 3 d and then were stimulated for 72 h under hypoxia. Morris water maze was used to investigate the learning and memory behaviors. Immunohistochemical staining and Western blotting were used to detect the SIRT1 expression. Results: The escape latency in crocin-1 groups was shorter than that in hypoxia model group, while the frequency of bestriding platform was increased (P < 0.05). Immunohistochemical staining and Western blotting both showed that the expression level of SIRT1 was higher in crocin-1 groups than that in hypoxia model group (P < 0.05), and the expression levels in mid- and high-dose groups were obviously higher. Conclusion: Crocin-1 could increase the expression of SIRT1 in hippocampus of rats, which maybe one of the important mechanisms for crocin-1 improving learning and memory function of SD rats under acute hypoxia.
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Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% N2 and 5% CO2, induction of cell hypoxia was confirmed based on increased intracellular Ca2+ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability (Po, up to 0.8). This channel was permeable to Na+ ions, but not to K+, Ca+, and Cl- ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated Na+ channel that can contribute to depolarization of the cell.
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Animals , Rats , Amiloride , Hypoxia , Blotting, Western , Cell Hypoxia , Epithelial Sodium Channels , Ion Channels , Ions , Neurons , Oxygen , PC12 Cells , PheochromocytomaABSTRACT
@#Objective To investigate the protective effect of berberine on acute hypoxia induced by sodium nitrite (NaNO2) in mice.MethodsThe animal model of acute hypoxia was established with NaNO2. Then the mice were treated with berberine by gavage in three different doses of 2.0 mg/kg, 4.0 mg/kg, and 8.0 mg/kg once everyday respectively for 6 days. The survival time according to the last breath, the breath time and open mouth times of animals were recorded. The superoxide dismutase (SOD), maleic dialdehyde (MDA), nitric oxide (NO) and lactic dehydrogenase (LDH) in brain tissue were tested. The pathological change was examined by HE staining.ResultsBerberine could significantly prolong the living time of acute hypoxia mice induced by NaNO2 and breath time after decapitation ( P<0.05, P<0.01), increase the activity of SOD and LDH, decrease the content of MDA and NO in brain tissue of hypoxia mice ( P<0.05, P<0.01). Under microscope, there were meningorrhagia, cellular necrosis in brain tissues of model animals, but no pathological changes found in berberine-treated animals.ConclusionBerberine has certain protective effect on acute hypoxia induced by NaNO2 in mice.
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Objective: To study the effect of acute hypoxia with simulated high altitude on the expression of orexins in rats hypothalamus. Methods: Rats were exposed to different high altitude(3 000 m,(4 000) m,5 000 m and 6 000 m for 8 h daily) in a hypobaric chamber.The expression of orexins in rat hypothalamus was determined by immunohistochemistry and the pathology changes of rat hypothalamus was observed with transelectricity. Results: The number of orexin-A immunoreactive positive cells in hypothalamus decreased obviously with hypoxia for 1 day(P
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Objective To explore the effects of acute hypoxia on the expression of neuropeptide Y (NPY) mRNA in the rat hypothalamus. Methods A total of 78 Wistar rats were randomly divided into 13 groups ( n =6 in each group): control group and 12 experimental groups. Rats in the experimental groups were exposed to hypoxia in the hypobaric chamber simulating the altitudes of 3 000, 4 000, 5 000, and 6 000 m for 1, 2, and 3 d, respectively. The expression of NPY mRNA in the rat hypothalamus under the condition of acute hypoxia was detected by semi quantitative reverse transcription polymerase chain reaction (RT PCR). Results ① Expression of NPY mRNA was detected in the rat hypothalamus in the experimental groups and the control group. ② Under the condition of acute hypoxia for the same time, the expression of NPY mRNA in the rat hypothalamus showed the tendency of decrease at increasing altitudes; ③ At the same altitude, expression of NPY mRNA in the rat hypothalamus decreased gradually with the increasing time for acute hypoxia. Conclusion Acute hypoxia can decrease the expression of NPY mRNA in the rat hypothalamus.
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Objective To study the effects of acute low temperature and hypoxia on serum SOD and MDA of myocardial ischemia rabbit. Methods 24 rabbits were randomly divided into 3 groups, such as normally low tamperature and hypoxia group, myocardial ischemia normal temporature and normal oxygen group and myocardial ischemia low temporature and hypoxia group. Put myocardial ischemia rabbits into the condition in which low temperature(-10?2) ℃ and hypoxia (oxygen content 8.5% ) existed, superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents were measured after an hour. Results Serum SOD activity were decreased significantly in acute low temperature and hypoxia compared with normal temperature and normal oxygen pressure (P
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AIM Protective action of TMP on hearts and brains under the condition of the acute hypoxia was studied. METHODS On the device of mice acute hypoxia ,ability of tolerancing hypoxia of mice was investigated,and superoxide dismutase(SOD) and malondialdehyde(MDA) and nitric oxide(NO) contents in hearts and brains were measured.RESULTS TMP could make the resisting hypoxia action in mice strengthen significantly,and the action had a does dependent increase. TMP made SOD contents in hearts and brains in does dependent increase;MDA contents in hearts and brains were not notable in low does ,but TMP could decreased MDA contents in hearts and brains in middle and high does ( P
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Objective: To explore the effect of acute hypoxia on the appetite and expression of neuropeptide Y (NPY) in rat hypothalamus. Methods: Wistar rats were randomly divided into control group, 3 000 m group, 4 000 m group , 5 000 m group and 6 000 m group for different times (1d, 2d and 3d respectively) . The change of appetite was observed and the expression of NPY in hypothalamus of rats was measured by immunohistochemical method. Results: (1) After acute hypoxia, the appetite of rats decreased. (2) The expression of NPY of the test groups and the normal group was decreased in arcuatus, paraventricular and dorsal median nucleus of the hypothalamus after acute hypoxia. Conclusion: Acute hypoxia might inhibit feed intake of rats, and decreased expression of NPY in hypothalamus, which may be one of the important reasons for loss of appetite.
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A simple hypobaric unit was used to study the effect of yeast and ascorbic acid on enhancing the endurance of acute hypoxia in 86 rats. The animals were divided into 2 groups; an observed group on a diet containing 3% of yeast and 0.1% of ascorbic acid, and a control group on basal diet. All the animals were subjected to a simulated altitude of 10,000 to 12,000 m simultaneously. It was found that the survival rate of the observed group was significantly higher than that of the control group (p