Effect of acute hypoxia on respiration and brain stem blood flow in the piglet

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2-4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.     

缺氧条件下冻伤对大鼠微循环液血灌流量的影响

本文采用体重２００±２０ｇ健康雄性Ｗｉｓｔａｒ大鼠,随机分为平原冻伤（ＦＮ）组,急性缺氧冻伤（ＦＡＨ）组和缺氧习服缺氧冻伤（ＦＨＡＣ）组,实验观察了大鼠右后肢重度冻伤前后各组大鼠双后肢皮肤微循环灌流量的改变,结果表明,平原冻伤使大鼠以后肢微循环灌流量明显减少,提示局部重度冻伤对微循环的影响不只局限于冻区也涉及到对侧肢体,冻冻前ＦＡＨ组大鼠微循环灌流量已明显低于ＦＮ组,表明生缺氧时血容量进行代偿性的     

Effects of short-term and prolonged aerogenic hypoxia on gamma-glutamyl transpeptidase activity in the brain,liver, and biological fluids of young rats

Posthypoxic fluctuations in the levels of two excitatory amino acids, glutamate and aspartate, may be related to changes in mechanisms(s) which are responsible for their reuptake. As gamma-glutamyl transpeptidase (GGT) plays a role in mediating the uptake of glutamate and aspartate into various compartments of the brain, we studied changes in the activity of this enzyme in main regions of the brain in young and adult rats. We found a posthypoxic increase in bound GGT activity in some brain regions of 18-day-old animals after acute exposure, but no changes were observed after prolonged altitude hypoxia, with the exception of a decrease in cortical GGT activity. In contrast, acute hypoxia decreased GGT activity in the cortical capillaries to 59%, but prolonged hypoxic exposure was ineffective. However, the activity of soluble GGT in the cerebrospinal fluid of both groups of rats was several-times elevated in comparison with controls. At the same time, bound GGT activity was increased in the liver after acute or prolonged altitude hypoxia. The soluble GGT activity in plasma was only increased after prolonged exposure. Ninety days after prolonged hypoxic exposure the bound GGT activity was reduced in all brain regions to about 60–70% of controls (significantly higher in females than in males) as long-term developmental sequel from early postnatal hypoxia.     

Ventilatory acclimatization to hypoxia is not dependent on cerebral hypocapnic alkalosis

We previously demonstrated that, in awake goats, 6 h of hypoxic carotid body perfusion during systemic normoxia produced time-dependent hyperventilation that is typical of ventilatory acclimatization to hypoxia (VAH). The hypocapnic alkalosis that occurred could have produced VAH by inducing cerebral vasoconstriction and brain lactic acidosis even though systemic arterial normoxia was maintained. In the present study we tested the hypothesis that hypocapnic alkalosis is a necessary component of VAH. Goats were prepared so that one carotid body could be perfused, from an extracorporeal circuit, with blood in which gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Using this preparation we carried out 4 h of hypoxic carotid body perfusion while maintaining systemic arterial (and brain) normoxia in awake goats. Expired minute ventilation (VE) was measured while CO2 was added to inspired air to maintain normocapnia. Carotid body PCO2 and PO2 were maintained near 40 Torr during the 4-h carotid body perfusion. Control mean VE was 8.65 +/- 0.48 l/min (mean +/- SE). With acute carotid body hypoxia (30 min) VE increased to 21.73 +/- 2.02 l/min (P less than 0.05); over the ensuing 3.5 h of carotid body hypoxia, VE progressively increased to 39.14 +/- 4.14 l/min (P less than 0.05). These data indicate that neither cerebral hypoxia nor hypocapnic alkalosis are required to produce VAH. After termination of the 4-h carotid body stimulation, hyperventilation was not maintained in these studies, i.e., there was no deacclimatization. This suggests that acclimatization and deacclimatization are produced by different mechanisms.     

Formation of Central Mechanisms of Regulation of Mammalian Motor Functions: Dependence on Conditions of Embryonal Development

The paper summarizes results of studying the acute hypoxia model during pregnancy in rats. A relationship has been demonstrated between changes of conditions of embryonal development and formation in postnatal ontogenesis of molecular-cellular mechanisms of brain functioning and behavior of progeny. In animals exposed to hypoxia at the prenatal 13–14th day a delay of physiological development and formation of motor reactions has been revealed, which correlates with disturbances of structures of the sensorimotor brain system. Changes of properties of brain transmitter systems and signal transduction systems in the sensorimotor cortex and striatum as well as impairment of learning capability in adult animals were shown. The detected changes in development of an organism are due to disturbance of neurogenesis of the studied brain structures during the period of action of the pathological factor. The proposed model of acute hypoxia during pregnancy might also be effective for the search for, and testing of, new neuroprotective and nootropic drugs and for elaboration of strategy for treatment of pathology of the nervous system in children and adults submitted to prenatal hypoxia, as well as for correction of disturbances of nervous system functions, which develop in the process of aging.     

Changes in tissue monoamine oxidase activity and resistance to acute hypoxia in rats during stress

Male Wistar rats exposed to different stresses developed shifts in the brain and liver monoaminoxidase activity. In the so called "cognitive" stimulation, the activity was enhanced in the brain and reduced in liver. Mild stresses also enhanced the activity in the brain. Extreme stimulation (starch peritonitis) caused a significant diminishing of the activity in the brain. All the stress schedules accompanied by enhancement of the brain monoaminoxidase activity increased the rats' tolerance of acute hypoxic hypoxia. Negative correlations between the blood lactic acid contents and the brain monoaminoxidase activity were revealed in rats of both the control and the "cognitive" groups. The findings suggest a direct interrelationship between post-stress shifts of the brain monoaminoxidase activity and the hypoxia tolerance.     

Inosine, not adenosine, initiates endothelial glycocalyx degradation in cardiac ischemia and hypoxia

Ischemia/reperfusion and hypoxia/reoxygenation of the heart both induce shedding of the coronary endothelial glycocalyx. The processes leading from an oxygen deficit to shedding are unknown. An involvement of resident perivascular cardiac mast cells has been proposed. We hypothesized that either adenosine or inosine or both, generated by nucleotide catabolism, attain the concentrations in the interstitial space sufficient to stimulate A3 receptors of mast cells during both myocardial ischemia/reperfusion and hypoxia/reoxygenation. Isolated hearts of guinea pigs were subjected to either normoxic perfusion (hemoglobin-free Krebs-Henseleit buffer equilibrated with 95% oxygen), 20 minutes hypoxic perfusion (buffer equilibrated with 21% oxygen) followed by 20 minutes reoxygenation, or 20 minutes stopped-flow ischemia followed by 20 minutes normoxic reperfusion (n = 7 each). Coronary venous effluent was collected separately from so-called transudate, a mixture of interstitial fluid and lymphatic fluid appearing on the epicardial surface. Adenosine and inosine were determined in both fluid compartments using high-performance liquid chromatography. Damage to the glycocalyx was evident after ischemia/reperfusion and hypoxia/reoxygenation. Adenosine concentrations rose to a level of 1 μM in coronary effluent during hypoxic perfusion, but remained one order of magnitude lower in the interstitial fluid. There was only a small rise in the level during postischemic perfusion. In contrast, inosine peaked at over 10 μM in interstitial fluid during hypoxia and also during reperfusion, while effluent levels remained relatively unchanged at lower levels. We conclude that only inosine attains levels in the interstitial fluid of hypoxic and postischemic hearts that are sufficient to explain the activation of mast cells via stimulation of A3-type receptors.     

小鼠急性低氧暴露时脑微循环障碍的研究

本研究旨在通过急性减压缺氧状态下脑微循环改变的观察进一步探讨急性高原病的发生机理。实验采用鼠尾静脉注射吖啶橙荧光素作标记,落射荧光显微镜观察分析。结果表明,急性低氧状态下脑血管普遍扩张,但脑表面微血管的扩张大于脑深部微血管的扩张,微动脉的扩张大于微静脉的扩张;脑表面及深部的毛细血管开放数目增多、密度增加、间距缩小;脑血流随缺氧加重而变慢并有淤积;微血管周围有渗出及出血;神经细胞肿胀,胞浆内有空泡水肿。提示急性高原缺氧状态下脑微循环有明显障碍。     

Effects of Bilobalide on Hypoxia/Hypoglycemia-Stimulated Glutamate Efflux from Rat Cortical Brain Slices

The aim of this study was to investigate the effects of bilobalide, the postulated active constituent of Ginkgo biloba, on the release of glutamate elicited by hypoxia/hypoglycemia. Cortical slices were prepared from rat brain and perfused with normal artificial cerebrospinal fluid (aCSF) or aCSF made hypoxic by gassing with nitrogen, and hypoglycemic by removal of glucose. The perfusate was assayed for glutamate by HPLC. After 30 minutes, perfusion with hypoxic/hypoglycemic aCSF glutamate levels in the perfusate were increased approximately 5-fold. Bilobalide at 1, 10, and 100 M, when perfused together with hypoxic/hypoglycemic aCSF, significantly reduced the release of glutamate. This study suggests that the reported neuroprotective properties of bilobalide may, in part, be mediated through its ability to reduce glutamate efflux, thus leading to a decrease in the excitotoxic effects of this neurotransmitter.     

Effects of hypercapnia and NO synthase inhibition in sustained hypoxic pulmonary vasoconstriction

Background

Acute respiratory disorders may lead to sustained alveolar hypoxia with hypercapnia resulting in impaired pulmonary gas exchange. Hypoxic pulmonary vasoconstriction (HPV) optimizes gas exchange during local acute (0-30 min), as well as sustained (> 30 min) hypoxia by matching blood perfusion to alveolar ventilation. Hypercapnia with acidosis improves pulmonary gas exchange in repetitive conditions of acute hypoxia by potentiating HPV and preventing pulmonary endothelial dysfunction. This study investigated, if the beneficial effects of hypercapnia with acidosis are preserved during sustained hypoxia as it occurs, e.g in permissive hypercapnic ventilation in intensive care units. Furthermore, the effects of NO synthase inhibitors under such conditions were examined.

Method

We employed isolated perfused and ventilated rabbit lungs to determine the influence of hypercapnia with or without acidosis (pH corrected with sodium bicarbonate), and inhibitors of endothelial as well as inducible NO synthase on acute or sustained HPV (180 min) and endothelial permeability.

Results

In hypercapnic acidosis, HPV was intensified in sustained hypoxia, in contrast to hypercapnia without acidosis when HPV was amplified during both phases. L-N^G-Nitroarginine (L-NNA), a non-selective NO synthase inhibitor, enhanced acute as well as sustained HPV under all conditions, however, the amplification of sustained HPV induced by hypercapnia with or without acidosis compared to normocapnia disappeared. In contrast 1400 W, a selective inhibitor of inducible NO synthase (iNOS), decreased HPV in normocapnia and hypercapnia without acidosis at late time points of sustained HPV and selectively reversed the amplification of sustained HPV during hypercapnia without acidosis. Hypoxic hypercapnia without acidosis increased capillary filtration coefficient (Kfc). This increase disappeared after administration of 1400 W.

Conclusion

Hypercapnia with and without acidosis increased HPV during conditions of sustained hypoxia. The increase of sustained HPV and endothelial permeability in hypoxic hypercapnia without acidosis was iNOS dependent.     

Hypoxic regulation of the fetal cerebral circulation.

Fetal cerebrovascular responses to acute hypoxia are fundamentally different from those observed in the adult cerebral circulation. The magnitude of hypoxic vasodilatation in the fetal brain increases with postnatal age although fetal cerebrovascular responses to acute hypoxia can be complicated by age-dependent depressions of blood pressure and ventilation. Acute hypoxia promotes adenosine release, which depresses fetal cerebral oxygen consumption through action of adenosine on neuronal A1 receptors and vasodilatation through activation of A2 receptors on cerebral arteries. The vascular effect of adenosine can account for approximately half the vasodilatation observed in response to hypoxia. Hypoxia-induced release of nitric oxide and opioids can account for much of the adenosine-independent cerebral vasodilatation observed in response to hypoxia in the fetus. Direct effects of hypoxia on cerebral arteries account for the remaining fraction, although the vascular endothelium contributes relatively little to hypoxic vasodilatation in the immature cerebral circulation. In contrast to acute hypoxia, fetal cerebral blood flow tends to normalize during acclimatization to chronic hypoxia even though cardiac output is depressed. However, uncompensated chronic hypoxia in the fetus can produce significant changes in brain structure and function, alteration of respiratory drive and fluid balance, and increased incidence of intracranial hemorrhage and periventricular leukomalacia. At the level of the fetal cerebral arteries, chronic hypoxia increases protein content and depresses norepinephrine release, contractility, and receptor densities associated with contraction but also attenuates endothelial vasodilator capacity and decreases the ability of ATP-sensitive and calcium-sensitive potassium channels to promote vasorelaxation. Overall, fetal cerebrovascular adaptations to chronic hypoxia appear prioritized to conserve energy while preserving basic contractility. Many gaps remain in our understanding of how the effects of acute and chronic hypoxia are mediated in fetal cerebral arteries, but studies of adult cerebral arteries have produced many powerful pharmacological and molecular tools that are simply awaiting application in studies of fetal cerebral artery responses to hypoxia.     

Microcirculation characteristics in apparently healthy subjects during acute hypoxia and intermittent hypoxic training

The characteristics of the microcirculation in the forearm skin of 29 apparently healthy male volunteers were studied in acute hypoxia and during intermittent hypoxic training (IHT) using computer laser Doppler flowmetry. It was shown that short-term exposure of apparently healthy subjects to simulated acute hypoxia optimized the microcirculation owing to sympathetic innervation and concomitant rearrangement of microvascular tone regulation (activation of skin perfusion and reduction of blood flow through arteriovenular shunts when the neurogenic tone component increases). A second (placebo-controlled) series of experiments showed that long-term hypoxic preconditioning (20 IHT sessions) facilitated fixing of the adaptive dynamic rearrangements aimed at microcirculation improvement. The microvasculature response during acute hypoxia and a course of IHT depends on the initial sensitivity of subjects to simulated hypoxia. Significant perfusion enhancement in the tissues studied and microvascular tone normalization were observed in the subjects that were initially sensitive to hypoxia.     

Effect of increased concentrations of ca++ and mg++ in the fluid perfusing the cerebral ventricles, and hypoxia on evoked tongue jerks

Effect of increased concentrations of Ca++ and Mg++ in the fluid perfusing the cerebral ventricles, and hypoxia on evoked tongue jerks. Acta Physiol. Pol., 1978, 29 (1): 27-36. The infraorbital nerve, the sensory part of the trigeminal nerve, was stimulated in rats under chloralose anaesthesia. Electric stimuli of 0.2 Hz caused retractive movements of the stretched tongue. These evoked tongue jerks (ETJ) were recorded directly on a kymograph or on a linear recorder. Using a stereotaxic apparatus cannulas were inserted into both lateral ventricles of the brain for infusion of McIlwain-Rodnight's fluid at a rate of about 50 microliter/minute. The cannula for outflow of the perfusing fluid was inserted into the cerebellomedullary cistern. The ETJ was enhanced by 43%, on the average, during perfusion of the cerebral ventricles with solutions with fivefold increased concentration of calcium ions, and decreased by a mean value 24% when the perfusing solution contained a higher concentration of magnesium ions. After 10 min of breathing with increased respiratory dead space, which caused hypoxia and hypercapnia, the amplitude of ETJ diminished by 65%, on the average.     

Ventriculo–cisternal perfusion of twelve amino acids in the rabbit

The clearances of twelve amino acids from the ventricles during ventriculocisternal perfusion in the rabbit have been measured; uptake by the brain was also measured and this permitted the separate computation of loss to brain and loss to blood during the perfusion. Clearance under carrier-free conditions was greater than when a concentration of 5mM unlabeled amino acid was present in the perfusion fluid. Brain uptake was also usually reduced by the presence of unlabeled amino acid due presumably to suppression of accumulation by brain cells. Reduction of transport across the blood-brain barrier would tend to increase brain uptake, and there was some evidence for a balance between the two opposing tendencies. Inhibition of clearance of a given labeled amino acid could be brought about by unlabeled amino acids of different molecular species. In general, the amino acids fell into three categories: neutral, acidic, and basic, and there was some overlap between them; of the neutral amino acids the A- and L-classification of Christensen was valid, although once again there was some overlap. If, during ventriculo-cisternal perfusion of a labeled amino acid, the activity of this labeled amino acid in the blood was raised well above that in the inflowing perfusion fluid, the labeled amino acid continued to be cleared from the perfusion fluid, suggesting uphill transport. On this basis it was suggested that the normally low concentrations of amino acids in the cerebrospinal fluid (CSF), by comparison with those in plasma, were due to an active transport from the CSF to the blood. Substrate-facilitated transport, whereby the penetration of labeled amino acid into the perfusion fluid from blood could be accelerated by adding unlabeled amino acid to the perfusion fluid, or vice versa, was demonstrated.     

Brain glutamate metabolism during hypoxia and peripheral chemodenervation

Glutamate stimulates resting ventilation by altering neural excitability centrally. Hypoxia increases central ventilatory drive through peripheral chemoreceptor stimulation and may also alter cerebral perfusion and glutamate metabolism locally. Therefore the effect of hypoxia and peripheral chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer amidated central nervous system glutamate was studied in intact and chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer 13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)----glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia. At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l-1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/- 10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3 mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary glutamate concentration tended to be higher in denervated animals. There were no differences between mean glutamine and gamma-aminobutyric acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

急性缺氧增强豚鼠小脑前下动脉平滑肌细胞外向电流并抑制缝隙连接

本文旨在研究急性缺氧对微动脉血管平滑肌细胞(vascular smooth muscle cells,VSMCs)膜电生理特性的影响。分离出豚鼠小脑前下动脉(anterior inferior cerebellar artery,AICA)段,胶原酶A消化后用显微镊去除微动脉外层结缔组织,然后给予无糖低氧的灌流液,同时应用全细胞膜片钳技术观察VSMCs膜电流的变化。结果显示:(1)当钳制电压在40mV时,急性缺氧引起一个反应幅度为(36.4±9.2)pA的外向电流,细胞静息膜电位从(33.2±1.9)mV超极化到(38.4±1.5)mV。急性缺氧电压依赖性地增强VSMCs外向电流,主要增强0～+40mV电压区间的激活电流幅度,+40mV激活电流幅度从(650±113)pA增加到(1900±197)pA。背景灌流K+通道阻断剂tetraethylammonium(TEA,1mmol/L)后,急性缺氧对VSMCs外向电流的增强作用显著减小。(2)急性缺氧使AICA上VSMCs的细胞膜电阻(R input)从(234±63)MΩ增加到(1211±201)MΩ,细胞膜电容(C input)从(279.3±83.2)p...     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

腺苷在低氧适应家兔脑血流调节中的作用

本研究观察了腺苷在低氧适应家兔脑血流(CBF)调节中的作用。结果表明:缺氧时适应组CBF改变不明显,对照组CBF明显增加;缺氧时适应组脑腺苷的含量明显低于对照组,而脑腺苷酸的含量明显高于对照组;适应组脑微血管对腺苷的反应与对照组相近。提示缺氧时低氧适应家兔CBF改变不明显,同低氧适应后脑腺苷含量较低、腺苷酸含量较高有关。     

Chronic hypoxia increases fetoplacental vascular resistance and vasoconstrictor reactivity in the rat

An increase in fetoplacental vascular resistance caused by hypoxia is considered one of the key factors of placental hypoperfusion and fetal undernutrition leading to intrauterine growth restriction (IUGR), one of the serious problems in current neonatology. However, although acute hypoxia has been shown to cause fetoplacental vasoconstriction, the effects of more sustained hypoxic exposure are unknown. This study was designed to test the hypothesis that chronic hypoxia elicits elevations in fetoplacental resistance, that this effect is not completely reversible by acute reoxygenation, and that it is accompanied by increased acute vasoconstrictor reactivity of the fetoplacental vasculature. We measured fetoplacental vascular resistance as well as acute vasoconstrictor reactivity in isolated perfused placentae from rats exposed to hypoxia (10% O(2)) during the last week of a 3-wk pregnancy. We found that chronic hypoxia shifted the relationship between perfusion pressure and flow rate toward higher pressure values (by approximately 20%). This increased vascular resistance was refractory to a high dose of sodium nitroprusside, implying the involvement of other factors than increased vascular tone. Chronic hypoxia also increased vasoconstrictor responses to angiotensin II (by approximately 75%) and to acute hypoxic challenges (by >150%). We conclude that chronic prenatal hypoxia causes a sustained elevation of fetoplacental vascular resistance and vasoconstrictor reactivity that are likely to produce placental hypoperfusion and fetal undernutrition in vivo.     

NO-dependent mechanisms of adaptation to hypoxia.

In studying NO-dependent mechanisms of resistance to hypoxia, it was shown that (1) acute hypoxia induces NO overproduction in brain and leaves unaffected NO production in liver of rats; (2) adaptation to hypoxia decreases NO production in liver and brain; and (3) adaptation to hypoxia prevents NO overproduction in brain and potentiates NO synthesis in liver in acute hypoxia. Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30%. Nomega-nitro-L-arginine (L-NNA, 50 mg/kg, single dose, ip), a NO synthase inhibitor, and diethyl dithiocarbamate (DETC, 200 mg/kg, single dose, iv), a NO trap, increases this parameter 1.3 and 2 times, respectively. Adaptation to hypoxia developed against a background of accumulation of heat shock protein HSP70 in liver and brain. A course of DNIC reproduced the antihypoxic effect of adaptation. A course of L-NNA during adaptation hampered both accumulation of HSP70 and development of the antihypoxic effect. Therefore, NO and the NO-dependent activation of HSP70 synthesis play important roles in adaptation to hypoxia.