Transport ATPases in the erythrocytes of rats acclimatized to intermittent altitude hypoxia

The activity of Na+/K+- and Ca2+-ATPase and some allosteric properties of Na+/K+-ATPase were studied in whole erythrocytes and their membrane preparations (ghosts) from rats exposed to intermittent altitude hypoxia (10 and 24 exposures, 8 h/day in an altitude chamber, stepwise up to an altitude of 7,000 m). Ca2+-ATPase activity was increased both in whole erythrocytes and ghosts after the first phase of acclimatization (10 exposures). In a standard incubation medium (containing 3 mmol.l-1 MgCl2 ), Na+/K+-ATPase activity in the ghosts was also increased after the initial phase of acclimatization whereas in whole erythrocytes Na+/K+-ATPase was only decreased in the regression phase. At high MgCl2 concentrations (12 mmol.l-1) changes of Na+/K+-ATPase activity both in whole erythrocytes and in the ghosts followed similar time course with a pronounced increase in the first phase of acclimatization (10 exposures) followed by an abrupt drop (24 exposures) and then by a gradual normalization in the regression phase. Sensitivity of the enzyme to mounting MgCl2 concentrations was increased in the ghosts at the end of acclimatization and was decreased in whole erythrocytes during acclimatization and especially in the regression phase. It has been suggested that chronic altitude hypoxia leads to the alteration of cooperative interaction of the Na+/K+-ATPase subunits in the erythrocyte membrane and accumulation of some factor in the cells inhibiting this enzyme.     

Increased affinity to substrate in sarcolemmal ATPases from hearts acclimatized to high altitude hypoxia

It has been well documented that acclimatization to chronic high altitude hypoxia involves a complex of adaptation changes which are capable of protecting the myocardium in diverse situations such as in acute hypoxia, coronary occlusion-induced ischaemia or isoprenaline-induced calcium overload. Since many of the former changes concern membrane functions, namely those of the sarcolemma, the activities and kinetic properties of sarcolemmal Mg2+-, Ca2+- and (Na+ + K+)-ATPase were investigated in right heart ventricles of rats acclimatized to intermittent high altitude hypoxia simulated in a barochamber. In the course of the experiment, the ventricles were subjected to a special anoxic test in vitro. The high altitude induced increase in cardiac tolerance to anoxia was not accompanied by any preservation of the sarcolemmal ATPase activities. On the contrary, membrane preparations obtained from the right ventricles of hearts acclimatized to high altitude exhibited significantly lower ATPase activities in comparison to non-acclimatized controls. The significant diminution in Km values of ATPases established in acclimatized hearts points to an increase in the affinity of their active sites to ATP. The latter effect is in agreement with the lowered rate of both the decrease in ATPase activities and the reduction of contractility in acclimatized hearts during the anoxic test, as well as with the considerably improved postanoxic reparability of contractions as compared to the controls. It is being concluded that the sarcolemmal changes at the level of ATPases involved in ionic transport processes represent an integral part of the adaptation complex to chronic high altitude hypoxia.     

Hepatic amoebiasis at high altitude

Latent amoebiasis is aggravated at high altitude. Protean manifestations are common. Fever is usually absent. Liver tenderness is not a feature and may have to be specially elicited. Leucocytosis is rare. Bowel symptoms inspite of presence of intestinal ulcerations are usually absent. Response to treatment with emetine or chloroquin is unsatisfactory and relapse rate is high. These points may interest mountaineers and other sojourners to high altitude.     

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude

Gonzalez, Norberto C., Richard L. Clancy, Yoshihiro Moue,and Jean-Paul Richalet. Increasing maximal heart rate increases maximal O₂ uptake in ratsacclimatized to simulated altitude. J. Appl.Physiol. 84(1): 164-168, 1998.Maximal exerciseheart rate (HR_max) is reducedafter acclimatization to hypobaric hypoxia. The lowHR_max contributes to reducemaximal cardiac output(_max) andmay limit maximal O₂ uptake(O_{2 max}). Theobjective of these experiments was to test the hypothesisthat the reduction in_max afteracclimatization to hypoxia, due, in part, to the lowHR_max, limitsO_{2 max}. Ifthis hypothesis is correct, an increase in _max wouldresult in a proportionate increase inO_{2 max}. Rats acclimatized to hypobaric hypoxia [inspiredPO₂(PI_O2) = 69.8 ± 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PI_O2 = 71.7 ± 1.1 Torr) or normoxic conditions(PI_O2 = 142.1 ± 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach itsspontaneous HR_max, which was 505 ± 7 and 501 ± 5 beats/min in hypoxic and normoxic exercise,respectively; in the other exercise bout,HR_max was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an ~10% increase in_max, since theincrease in HR_max was offset by a10% decrease in stroke volume, probably due to shortening of diastolicfilling time. The increase in_max was accompanied by a proportionate increase in maximal rate of convective O₂ delivery(_max × arterial O₂ content), maximal workrate, and O_{2 max} inhypoxic and normoxic exercise. The data show that increasingHR_max topreacclimatization levels increasesO_{2 max}, supportingthe hypothesis that the lowHR_max tends to limitO_{2 max} after acclimatization to hypoxia.

     

Hepatic gluconeogenesis in chickens

Summary Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate in starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo.The alteration of the NADH/NAD⁺ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP.Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level.Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.     

Myocardial hypertrophy in rats exposed to simulated high altitude

Myocardial hypertrophy in Sprague-Dawley adult rats exposed to hypobaric hypoxia (0.40 atmosphere of air/18 h daily for 7 days) in a hypobaric chamber was investigated. Changes in the myocardial mass were evaluated on the basis of the dry heart weight and expressed as mg/100 g of total body weight (mean +/- SEM). Data are presented indicating that: chronic hypobaric hypoxia causes a significant degree of myocardial hypertrophy in rats; hypertrophic process involves both ventricles (the right more than the left); removal of the hypoxic stimulus leads to the disappearance of hypertrophy when evaluated as an increase in dry heart weight; hypoxia affects the synthesis of a significant amount of connective tissue in the left ventricle, which is not exposed to pressure load. The r?le of neurohumoral factors (i.e., adrenergic stimulation and catecholamines) in the development of the ventricular hypertrophy is suggested.     

Inhibition of renal gluconeogenesis in rats by ochratoxin.

In kidney-cortex slices from rats fed on 2.0 mg of ochratoxin A/kg per day for 2 days, gluconeogenesis from pyruvate is decreased by 26%, and renal phosphoenolpyruvate carboxykinase activity is lowered by about 55%. Gluconeogenesis from 10 mM-lactate or 20 mM-malate or -glutamine is also significantly decreased. Hepatic phosphoenolpyruvate carboxykinase is unchanged or increased, and hexokinase activity in kidney and liver remains unaffected. We conclude that ochratoxin A in vivo is an inhibitor of renal phosphoenolpyruvate carboxykinase activity, which is responsible, at least in part, for the block in renal gluconeogenesis.     

Effect of acetazolamide on cytokines in rats exposed to high altitude

Acute mountain sickness (AMS) is a dangerous hypoxic illness that can affect humans who rapidly reach a high altitude above 2500 m. In the study, we investigated the changes of cytokines induced by plateau, and the acetazolamide (ACZ) influenced the cytokines in rats exposed to high altitude. Wistar rats were divided into low altitude (Control), high altitude (HA), and high altitude + ACZ (22.33 mg/kg, Bid) (HA + ACZ) group. The rats were acute exposed to high altitude at 4300 m for 3 days. The HA + ACZ group were given ACZ by intragastric administration. The placebo was equal volume saline. The results showed that hypoxia caused the heart, liver and lung damage, compared with the control group. Supplementation with ACZ significantly alleviated hypoxia-caused damage to the main organs. Compared with the HA group, the biochemical and blood gas indicators of the HA + ACZ group showed no difference, while some cytokines have significantly changed, such as activin A, intercellular adhesion molecule-1 (ICAM-1, CD54), interleukin-1α,2 (IL-1α,2), l-selectin, monocyte chemotactic factor (MCP-1), CC chemokines (MIP-3α) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). Then, the significant difference pro-inflammatory cytokines in protein array were chosen for further research. The protein and mRNA content of pro-inflammatory cytokines MCP-1, interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), interferon-γ (IFN-γ) in rat lung were detected. The results demonstrated that the high altitude affected the body’s physiological and biochemical parameters, but, ACZ did not change those parameters of the hypoxia rats. This study found that ACZ could decrease the content of pro-inflammatory cytokines, such as MCP-1, IL-1β, TNF-α and IFN-γ in rat lungs, and, the lung injury in the HA + ACZ group reduced. The mechanism that ACZ protected hypoxia rats might be related to changes in cytokine content. The reducing of the pro-inflammatory cytokines in rat lung might be other reason to explain ACZ against the acute mountain sickness.     

Strain and sex differences in the cardiopulmonary adaptation of rats to high altitude

On chronic exposure to hypoxia, the commercially available Hilltop (H) strain of male Sprague-Dawley rats develops severe pulmonary hypertension, right ventricular hypertrophy (RVH), and polycythemia. These signs of chronic mountain sickness are associated with a high mortality rate. In contrast, the Madison (M) strain of Sprague-Dawley rats remains healthy with significantly less severe cardiopulmonary and hematological responses. Breeding experiments under locally controlled conditions were undertaken to determine if the differences between the two strains were genetically determined and to look for possible sex differences. Following 30 to 50 days exposure to a simulated altitude of 18,000 ft, the first generation of male H rats exhibited a higher right ventricular peak systolic pressure (RVPP), a more pronounced RVH, and a greater degree of polycythemia than the male M rats. The H rats had a mortality rate of 40% in contrast to a rate of 0% in the male M rats. The first generation of female H rats also developed a higher RVPP, a greater RVH, and more severe polycythemia than that in the female M rats. There were no differences in RVPP or RVH between the males and females of either strain. Females of both strains tolerated the hypoxic exposure with a 0% mortality rate. The data suggest that the differences between the males of H and M strains in their cardiopulmonary and hematological responses and in their susceptibilities to chronic hypoxia are genetic in nature. They further suggest that the female resistance to hypoxia is not due to milder cardiopulmonary responses. Perhaps female rats tolerate RVH better than male rats, at least of the H strain.