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At least 19 recordsLinked to original sources
PubMed1984

Interacting effects of hypoxia adaptation and acute hypercapnia on oxygen tolerance in rats.

To define the effects of hypoxia adaptation on tolerance to a useful range of O2 pressures, groups of 20 or more rats were exposed to O2 at 1.0, 1.5, 2.0, 3.0, and 4.0 ATA before and after adaptation to an inspired PO2 (PIO2) of 71 Torr for 5 days. Effects of acute hypercapnia on O2 tolerance in hypoxia-adapted rats were also determined by exposing rats to the same O2 pressures with an inspired PCO2 (PICO2) of 60 Torr. In nonadapted rats exposed to O2 at 1.0, 1.5, 2.0, 3.0, and 4.0 ATA, 50% mortality (LD50) occurred at 76.4, 26.8, 17.4, 9.0, and 6.4 h, respectively. LD50 values in O2-CO2 at the same pressures were 77.1, 24.5, 15.6, 3.4, and 1.7 h. Hypoxia-adapted rats had only 20% mortality in O2 at 1.0 ATA, and survivors were killed at 336 h. In O2-CO2 at 1.0 ATA, mortality was 85% with an LD50 at 282 h. LD50 values in hypoxia-adapted rats at O2 pressures of 1.5, 2.0, 3.0, and 4.0 ATA were 63.1, 22.5, 7.9, and 3.8 h, respectively. Corresponding values in O2-CO2 were 29.5, 18.7, 4.9, and 1.9 h. Exposure to O2 at 4.0 ATA caused nearly immediate onset of violent convulsions in hypoxia-adapted rats compared with a 50% incidence of convulsions at 3.2 h in nonadapted rats. These data indicate that hypoxia-adaptation increases pulmonary O2 tolerance but reduces central nervous system (CNS) O2 tolerance. However, the enhanced pulmonary O2 tolerance in hypoxia-adapted rats is greatly diminished when acute hypercapnia is superimposed on O2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1998

C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia-adapted rats.

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test the hypothesis that C-type natriuretic peptide (CNP) also modulates pulmonary vascular responses to hypoxia, we compared the vasodilator effect of CNP with that of ANP on pulmonary arterial rings, thoracic aortic rings, and isolated perfused lungs obtained from normoxic and hypoxia-adapted rats. We also measured CNP and ANP levels in heart, lung, brain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP mRNA levels were quantified in the same organs by relative RT-PCR. CNP was a less potent vasodilator than ANP in preconstricted thoracic aortic and pulmonary arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats. Chronic hypoxia increased plasma CNP (15 +/- 2 vs. 6 +/- 1 pg/ml; P < 0.05) and decreased CNP in the right atrium (35 +/- 14 vs. 65 +/- 17 pg/mg protein; P < 0.05) and in the lung (3 +/- 1 vs. 14 +/- 3 pg/mg protein; P < 0.05) but had no effect on CNP in brain or right ventricle. Chronic hypoxia increased ANP levels fivefold in the right ventricle (49 +/- 5 vs. 11 +/- 2 pg/mg protein; P < 0.05) but had no effect on ANP in lung or brain. There was a trend toward decreased ANP levels in the right atrium (2,009 +/- 323 vs. 2,934 +/- 397 pg/mg protein; P = not significant). No differences in CNP transcript levels were observed between the two groups of rats except that the right atrial CNP mRNA levels were lower in hypoxia-adapted rats. We conclude that CNP is a less potent pulmonary vasodilator than ANP in normoxic and hypoxia-adapted rats and that hypoxia raises circulating CNP levels without increasing cardiopulmonary CNP expression. These findings suggest that CNP may be less important than ANP or BNP in protecting against hypoxic pulmonary hypertension in rats.

Animals↗
PubMed1988

Lung MK 351A uptake after hypoxia adaptation and subsequent hyperoxia exposure.

This study investigated the effects of hypoxia adaptation (10% O2 for 4 days) on rat lung angiotensin-converting enzyme (ACE) content before and after hyperoxia exposure (greater than 95% O2 for 2 days). The rationale for this investigation was that hyperoxia exposure decreases lung ACE, while hypoxia adaptation produces tolerance (improved survival) to oxygen toxicity in rats. Rats were exposed to air, hypoxia, hyperoxia alone, or hypoxia followed immediately by hyperoxia. The lungs were then excised and perfused in vitro at 12 ml/min with buffer. Lung ACE content was quantitated by measuring the single-pass binding of an iodinated ACE inhibitor, 125I-MK 351A, a derivative of lisinopril. We showed previously that 125I-MK 351A binding correlates quantitatively with ACE activity in lung homogenates and isolated, perfused lungs. Lung internal surface area was estimated by measuring the mean alveolar diameter of 5 micron hematoxylin and eosin sections from lungs fixed in inflation (25 cmH2O transpulmonary pressure). Hypoxia adaptation per se had no effect on 125I-MK 351A binding or estimated alveolar surface area, while hyperoxia exposure caused a significant decrease in both 125I-MK 351A binding and alveolar surface area. These hyperoxia-induced decreases were prevented partially by hypoxia adaptation, indicating a protective effect on both ACE content and surface area. 125I-MK 351A binding in isolated perfused lungs changed in parallel with histologically estimated surface area. These results indicate that hypoxia preadaptation minimizes the oxygen-induced decrease in lung microvascular ACE content.

Animals↗
PubMed1988

Altered angiotensin-converting enzyme in lung and extrapulmonary tissues of hypoxia-adapted rats.

The effects of exposing rats to hypoxia (10% O2) at normal atmospheric pressure for periods of 14 or 28 days on angiotensin-converting enzyme (ACE) activity and stores of angiotensin I (ANG I) and angiotensin II (ANG II) in lung, kidney, brain, and testis were examined. ACE activity was measured by spectrophotometric assay, and active sites of ACE were estimated by measuring the binding of 125I-351A [N-(1-carbonyl-3-phenyl-propyl)-L-lysyl-L-proline], a highly specific active site-directed inhibitor of ACE, to tissue homogenates and perfused lungs. Hypoxia exposure produced progressive reductions in ACE activity in lung homogenates and in ACE inhibitor binding to perfused lungs. ANG II levels in lungs from hypoxia-adapted animals were significantly less than air controls, suggesting that the reduction in intrapulmonary ACE activity was associated with reduced local generation of ANG II. ACE activity was increased in kidney and unchanged in brain and testis of hypoxia-adapted rats compared with air controls. Thus the effects of chronic hypoxia on catalytically active ACE and ACE active sites in the intact animal were organ specific. Adaptation to chronic hypoxia did not significantly alter plasma renin activity or ANG I or ANG II levels or serum ACE content. The hypoxia-induced alterations in lung and kidney ACE were reversible after return to a normoxic environment.

Adaptation, Physiological↗
PubMed2005

Effects of acute and adaptive hypoxia on heat shock protein expression in hepatic tissue.

This experimental study was designed to analyze the expression of heat shock protein (HSP) in hepatic tissue induced by acute and adaptive hypoxic hypoxia. Rabbits were exposed to 5000 m simulated altitude at 11% O(2) in a chamber. Total antioxidant status (TAS) plasma content showed a significant decrease in the acute and adaptive hypoxia groups compared with the control group. Regarding TAS, there was no statistically significant difference between the acute and adaptive hypoxia groups. Histopathological evidence of liver injury was observed in study groups. Immunohistochemical analysis showed diffuse HSP70 staining in the hepatocytes in acute hypoxia group. Staining was focal and prominent in pericentral hepatocytes in the adaptive hypoxia group. As HSP expression appeared increased, total injury score increased as well. There was an inverse correlation between HSP and TAS, but it did not reach statistical value. Our results confirmed the expression of HSP in hepatic tissue related to defense against cellular injury in a hypoxia model. It is an early response in acute hypoxia and may decrease in adaptive hypoxia. It seems that HSP is induced, rather than protectively, as an early marker of liver injury. HSP70 induction and overexpression seem to be, at least in part, explained by impaired antioxidant defense mechanisms.

Acute Disease↗
PubMed1999

Production and storage of nitric oxide in adaptation to hypoxia.

Adaptation to hypobaric hypoxia is known to exert multiple protective effects related with nitric oxide (NO). However the effect of adaptation to hypoxia on NO metabolism has remained unclear in many respects. In the present work we studied the interrelation between NO production and storage in the process of adaptation to hypoxia. The NO production was determined by the total nitrite/nitrate concentration in rats plasma. The volume of NO store was evaluated in vitro by the magnitude of isolated aorta relaxation to diethyldithiocarbamate. It was shown that both the nitrite/nitrate level and the NO store increased as adaptation to hypoxia developed. Furthermore, the NO store volume significantly correlated with plasma nitrite/nitrate. Therefore, adaptation to hypoxia stimulates NO production and storage and these effects can potentially underlie NO-dependent beneficial effects of adaptation.

Adaptation, Physiological↗
PubMed1988

Atrial natriuretic peptide lowers pulmonary arterial pressure in hypoxia-adapted rats.

To test the hypothesis that atrial natriuretic peptide (ANP) has a direct vasodilator effect on the pulmonary vasculature that is enhanced in hypoxia-induced pulmonary hypertension in the rat, we determined the effects of ANP on mean pulmonary (MPAP) and systemic arterial pressure (MSAP) in intact conscious Sprague-Dawley rats exposed to 10% O2 or room air for 4 wk. Catheters were placed in the pulmonary artery through the right jugular vein by means of a closed-chest technique. MPAP and MSAP were monitored before and after intravenous injections of graded doses of ANP. ANP produced dose-related decreases in MPAP that were greater in the hypoxic group than in air controls. There were no significant between-group differences in the systemic depressor responses to ANP or in the ANP-induced reduction in cardiac output. ANP lowered MPAP significantly in isolated perfused lungs from both hypoxia-adapted and air control rats, and this effect was significantly greater in the hypoxic than the air control lungs. These data indicate that ANP lowers pulmonary arterial pressure in rats with hypoxia-induced pulmonary hypertension, mainly by a direct vasodilator effect on the pulmonary vasculature.

Animals↗
PubMed2000

Role of nitric oxide in adaptation to hypoxia and adaptive defense.

Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.

Adaptation, Physiological↗
PubMed2006

Proteomic analysis of plasma membrane from hypoxia-adapted malignant melanoma.

Hypoxic conditions often persist within poorly vascularized tumors. At the cellular level constitutive activation of transcriptional regulators of the hypoxic response leads to the emergence of clones with aggressive phenotypes. The primary interface between the cell and the hypoxic environment is the plasma membrane. A detailed investigation of this organelle is expected to yield further targets for therapeutic perturbation of the response to hypoxia. In the present study, quantitative proteomic analysis of plasma membrane from hypoxia-adapted murine B16F10 melanoma was performed using differential 16O/18O stable isotopic labeling and multidimensional liquid chromatography-tandem mass spectrometry. The analysis resulted in the identification of 24,853 tryptic peptides, providing quantitative information for 2,433 proteins. For a subset of plasma membrane and secreted proteins, quantitative RT-PCR was used to gain further insight into the genomic regulatory events underlying the response to hypoxia. Consistent increases at the proteomic and transcriptomic levels were observed for aminopeptidase N (CD13), carbonic anhydrase IX, potassium-transporting ATPase, matrix metalloproteinase 9, and stromal cell derived factor I (SDF-1). Antibody-based analysis of a panel of human melanoma cell lines confirmed that CD13 and SDF-1 were consistently upregulated during hypoxia. This study provides the basis for the discovery of novel hypoxia-induced membrane proteins.

Amino Acid Sequence↗
PubMed2000

[Nitric oxide storage in rats of various genetic strains and its role in the antistressor effect of adaptation to hypoxia].

Adaptation to hypobaric hypoxia induced a gradual increase in the NO production along with a progressive NO storage in vascular wall. Unadapted August rats were more resistant against stress-induced stomach ulceration than the Wistar rats. Following a 6-day adaptation rats of both strains revealed a protective antiulcerogenic effect. A long-term adaptation potentiated the stress damage of the stomach rather than protected against it. A higher basal NO production seems to provide a more efficient antistress defence in the August rats. An intense NO storage may create a relative NO shortage and thus predispose to stress-induced vasoconstriction and ulceration.

Adaptation, Physiological↗
PubMed2006

Renal parenchymal oxygenation and hypoxia adaptation in acute kidney injury.

The pathogenesis of acute kidney injury (AKI), formally termed acute tubular necrosis, is complex and, phenotypically, may range from functional dysregulation without overt morphological features to literal tubular destruction. Hypoxia results from imbalanced oxygen supply and consumption. Increasing evidence supports the view that regional renal hypoxia occurs in AKI irrespective of the underlying condition, even under circumstances basically believed to reflect 'direct' tubulotoxicity. However, at present, it is remains unclear whether hypoxia per se or, rather, re-oxygenation (possibly through reactive oxygen species) causes AKI. Data regarding renal hypoxia in the clinical situation of AKI are lacking and our current concepts regarding renal oxygenation during acute renal failure are presumptive and largely derived from experimental studies. There is robust experimental evidence that AKI is often associated with altered intrarenal microcirculation and oxygenation. Furthermore, renal parenchymal oxygen deprivation seems to participate in the pathogenesis of experimental AKI, induced by exogenous nephrotoxins (such as contrast media, non-steroidal anti-inflammatory drugs or amphotericin), sepsis, pigment and obstructive nephropathies. Sub-lethal cellular hypoxia engenders adaptational responses through hypoxia-inducible factors (HIF). Forthcoming technologies to modulate the HIF system form a novel potential therapeutic approach for AKI.

Adaptation, Physiological↗
PubMed1975

[Dynamics of nucleic acid and protein concentration and synthesis during adaptation to hypoxia].

Adaptation of female Wistar rats to hypoxia was carried out in the altitude chamber (barochamber) for 40 days, 6 hours per day at the altitude of 7,000 meters. By the end of the adaptation the relative weight of the lungs increased by 37 per cent (this seeming to indicate hypertrophy of the lungs), and the concentration of RNA in the lung tissue increased by 30 per cent; at the same time the RNA concentration in the lungs as a whole increased by 85 per cent DNA concentration in the lung tissue showed no essential change, and its content in the lungs increased at the same rate as the lungs' weight. An increase in protein synthesis in the lungs determined by the S-35-methionine incorporation constituted 133% in the adapted rats in comparison with control.

Adaptation, Physiological↗
PubMed2005

Hypoxia adaptation and hemoglobin mutation in Tibetan chick embryo.

Tibetan chick lives at high altitudes between 2600 and 4200 m with a high hatchability and low land breeds survive rarely with a hatchability of 3.0% under hypoxia of simulated 4200 m. Under hypoxia of whole 21 d, the hatchability of Tibetan chick and Recessive White Feather broiler differed with a greatest disparity from day 4 to 11 and also significantly in other stages except from day 1 to 3. Hypoxia in each stage did not reduce significantly survival rate of this stage except hatchability. These two results indicated that the hypoxia in the early stage had an adverse effect on the later stage. All exons encoding chick hemoglobins were sequenced to analyze gene polymorphism. The functional mutation Met-32(B13)-Leu, related with hypoxia, was found in alphaD globin chain and the mutation frequency increased with increased altitude. In addition, under hypoxic conditions, the population with higher mutation frequency had a higher hatchability. The automated homology model building was carried out using crystal structure coordinates of chick HbD. The results indicated that the substitution Met-32(B13)-Leu provides a more hydrophobic environment which leads to higher stability of heme and oxygen affinity of hemoglobin. The occurrence of the mutation Met-32(B13)-Leu is related to the origin of Tibetan chick.

Adaptation, Physiological↗
PubMed1991

Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: a comparison in control and hypoxia-adapted animals.

1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2 alpha. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 micrograms) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P less than 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P less than 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗