Biomedical subjects

R Motais

Publications and source records attributed to R Motais.

At least 37 records · Page 2Linked to original sources

PubMed1991

Red cell volume regulation: the pivotal role of ionic strength in controlling swelling-dependent transport systems.

A volume increase of trout erythrocytes can be induced either by beta-adrenergic stimulation of a Na+/H+ antiport in an isotonic medium (isotonic swelling) or by suspending red cells in an hypotonic medium (hypotonic swelling). In both cases cells regulate their volume by a loss of osmolytes via specific pathways. After hypotonic swelling several volume-dependent pathways were activated allowing K+, Na+, taurine and choline to diffuse. All these pathways were fully inhibited by furosemide and inhibitors of the anion exchanger (DIDS, niflumic acid), and the K+ loss was mediated essentially via a 'Cl(-)-independent' pathway. After isotonic swelling, the taurine, choline and Na+ pathways were practically not activated and the K+ loss was strictly 'Cl(-)-dependent'. Thus cellular swelling is a prerequisite for activation of these pathways but, for a given volume increase, the degree of activation and the degree of anion-dependence of the K+ pathway depend on the nature of the stimulus, whether hormonal or by reduction of osmolality. It appears that the pattern of the response induced by hormonal stimulation is not triggered by either cellular cAMP (since it can be reproduced in the absence of hormone by isotonic swelling in an ammonium-containing saline) or by the tonicity of the medium in which swelling occurs since after swelling in an isotonic medium containing urea, the cells adopt the regulatory pattern normally observed after hypotonic swelling. We demonstrated that the stimulus is the change in cellular ionic strength induced by swelling: when ionic strength drops, the cells adopt the hypotonic swelling pattern; when ionic strength increases, the isotonic swelling pattern is activated. To explain this modulating effect of ionic strength a speculative model is proposed, which also allows the integration of two further sets of experimental results: (i) all the volume-activated transport systems are blocked by inhibitors of the anion exchanger and (ii) a Cl(-)-dependent, DIDS-sensitive K+ pathway can be activated in static volume trout red cells (i.e., in the absence of volume increase) by the conformational change of hemoglobin induced by the binding of O2 or CO to the heme.

Ammonium Chloride↗

PubMed1991

Regulation of Cl-dependent K transport by oxy-deoxyhemoglobin transitions in trout red cells.

The oxygenation of trout red cells opens a Cl-dependent K pathway inhibited by furosemide, and by inhibitors of the erythrocyte anion exchanger such as DIDS and niflumic acid. The trigger is the deoxy-oxy conformational change of hemoglobin. The binding of carbon monoxide to heme, which induces a similar conformational change, mimics the effect of oxygen. The possible mechanisms enabling molecular oxygen to control the transport protein are discussed. This oxygenation-activated K transport appears to play a regulatory role in the control of the extracellular K concentration.

Animals↗

PubMed1991

Cell volume regulation by trout erythrocytes: characteristics of the transport systems activated by hypotonic swelling.

1. An osmolality reduction of the suspending medium leads to osmotic swelling of trout erythrocytes, which is followed by a volume readjustment towards the original level. The regulatory volume decrease (RVD) was not complete after 1 h. 2. During RVD the cells lost K+ and Cl- but gained Na+. This entry of Na+, which is about half the K+ loss, explains the incomplete volume recovery (it was complete when Na+ was replaced by impermeant N-methyl-D-glucamine). The cells also lose large quantities of taurine, which accounts for about 53% of the volume recovery. In addition RVD is accompanied by the activation of a pathway allowing some large organic cations which are normally impermeant, such as choline or tetramethyl-ammonium, to rapidly penetrate the cells. 3. The swelling-activated K+ loss is not significantly affected by replacement of Cl- by NO3-, indicating that K+ moves through a Cl(-)-independent K+ pathway. Furosemide, DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) and niflumic acid inhibit the K+ loss. From experiments performed in high-K(+)-containing media, it appears that these compounds block the K+ flux, not by inhibiting Cl- movements but by interfering with the K+ pathway. 4. All the volume-activated pathways (K+, Na+, taurine, choline) are fully inhibited by furosemide and by inhibitors of the anion exchanger such as DIDS and niflumic acid. The concentration required for 50% inhibition (IC50) of both inorganic cations and taurine appears to be similar. It is proposed that DIDS interacts with a unique target which controls all the volume-sensitive transport systems.

Amino Acids↗

PubMed1990

Arrestin from nucleated red blood cells binds to bovine rhodopsin in a light-dependent manner.

Using a panel of monoclonal antibodies, it has previously been demonstrated that the cytosol of nucleated red cells (trout and turkey) contains a protein similar to arrestin, a soluble protein found so far only in the photosensitive cells and which, by binding to photoexcited rhodopsin, inhibits the phototransduction process. The role of this arrestin-like protein in non-photosensitive cells is questionable. In this report we present evidence that partially purified red blood cell arrestin (RBC arrestin) behaves functionally like bovine retinal arrestin: it binds to phosphorylated bovine rhodopsin only when this receptor has been photoactivated. Thus RBC arrestin and bovine retinal arrestin are closely related both structurally and functionally. By analogy with the function of retinal arrestin, it is proposed that RBC arrestin is involved in desensitization of membrane transport proteins and/or adrenergic receptors.

Animals↗

PubMed1990

Catecholamine release controlled by blood oxygen tension during deep hypoxia in trout: effect on red blood cell Na/H exchanger activity.

Changes in plasma catecholamine levels were measured in trout exposed to acute hypoxia, in order to correlate with acid-base disturbances due to activation of the cAMP-dependent Na+/H+ antiporters of red blood cells, as previously described (Fiévet B., Respir. Physiol. 74, 99-114, 1988). The extracellular acidosis corresponding with the stimulation of the exchangers, occurred when arterial oxygen partial pressure (PaO2) reached around 15 Torr (Thomas S., Respir. Physiol. 74, 77-90, 1988). This blood pH drop coincided with a marked increase in plasma catecholamine levels. The catecholamine secretion was transient and the hormones were cleared provided PaO2 remained above 10 Torr. On the other hand, when PaO2 remained below 10 Torr, there was a persistent secretion of catecholamines. This is in agreement with the fact that the exchangers are 'turned off' or sustained when PaO2 remains above or below 10 Torr respectively, as previously described. Following the transient hormone peak when PaO2 stabilized above 10 Torr, it was possible to trigger the second pattern of continuous catecholamine secretion by controlling water PO2 so that PaO2 declined below 10 Torr. We conclude that the blood oxygen level controls catecholamine secretion during deep hypoxia.

Acid-Base Imbalance↗

PubMed1990

Effects of anions on the Na(+)-H+ exchange of trout red blood cells.

1. Replacement of chloride by foreign anions in the suspending medium of trout erythrocytes can affect in a complex manner both the activation by catecholamines of the latent Na(+)-H+ exchanger and its subsequent desensitization. These changes are discussed in relation to other cellular modifications (distribution of permeant anions and accumulation of cyclic AMP) induced by foreign anions. 2. The transfer of trout erythrocytes from a chloride-containing medium to media containing lyophilic permeable anions, NO3- or SCN-, immediately induces a decrease of distribution ratios of permeable anions across the red cell membrane (i.e. Donnan ratios). It is probable that the binding of lyophilic anions to haemoglobin, by altering the amount of negative fixed charges, results in changes of distribution of permeant anions across the membrane. 3. The effectiveness of anions in decreasing both the activation of the Na(+)-H+ exchanger and the Donnan ratio follows the same sequence in both cases, i.e., SCN- greater than NO3- greater than Cl- = propionate. It was demonstrated that a change in Donnan ratio affects antiport activity possibly through a shift in intracellular pH; such a mechanism however cannot account for all the effects of foreign anions on antiport activity. 4. The present results show that lyophilic anions do not modify the affinity of the antiporter for sodium ions but greatly decrease the transport capacity of the exchange system. This is interpreted as indicating that the binding of lyophilic anions to some component of the transport system prevents antiporters from establishing their activated configuration once stimulated. Since the inhibitory effect of anions on Na(+)-H+ exchange has been demonstrated in all erythrocytes studied but in no other cell, the crucial substance involved in this inhibition could well be haemoglobin, which appears to control antiport activity in erythrocytes. 5. Some anions affect desensitization of the exchanger. This effect is not related to the lyophilic character of the anion and is not mediated by a change in intracellular cyclic AMP. 6. Propionate and acetate drastically reduce the intracellular level of cyclic AMP and seem to facilitate the activated configuration of the exchanger.

Animals↗

PubMed1989

Immunological detection of arrestin, a phototransduction regulatory protein, in the cytosol of nucleated erythrocytes.

Cytosolic extracts of trout and turkey erythrocytes were tested for their immunoreactivity with polyclonal and monoclonal antibodies to retinal arrestin (S-antigen), a cytosolic protein of photoreceptor cells involved in the desensitization of rhodopsin. After adsorption or immunoaffinity chromatography of the extracts, these antibodies specifically recognized a protein having a molecular weight similar to that of retinal arrestin. Because the G-protein-mediated transduction systems, such as visual and beta-adrenergic systems, display a high degree of structural and functional homology, the presence of arrestin-like proteins in non-photosensitive cells suggests that these proteins are involved in the transduction of chemical signals, with a possible role in receptor desensitization.

Animals↗

PubMed1989

Glutaraldehyde fixation of the cAMP-dependent Na+/H+ exchanger in trout red cells.

It has been shown that the addition of a beta-adrenergic catecholamine to a trout red blood cell suspension induces a 60-100-fold increase of sodium permeability resulting from the activation of a cAMP-dependent Na+/H+ antiport. Subsequent addition of propranolol almost instantaneously reduces the intracellular cAMP concentration, and thus the Na permeability, to their basal values (Mahé et al., 1985). If glutaraldehyde (0.06-0.1%) is added when the Na+/H+ exchanger is activated after hormonal stimulation, addition of propranolol no longer inhibits Na permeability: once activated and fixed by glutaraldehyde, the cAMP dependence disappears. Glutaraldehyde alone causes a rapid decrease in the cellular cAMP concentration. In its fixed state the antiporter is fully amiloride sensitive. The switching on of the Na+/H+ exchange by cAMP is rapidly (2 min) followed by acute but progressive desensitization of the exchanger (Garcia-Romeu et al., 1988). The desensitization depends on the concentration of external sodium, being maximal at a normal Na concentration (145 mM) and nonexistent at a low Na concentration (20 mM). If glutaraldehyde is added after activation in nondesensitizing conditions (20 mM Na), transfer to a Na-rich medium induces only a very slight desensitization: thus the fixative can "freeze" the exchanger in the nondesensitizing conformation. NO3- inhibits the activity of the cAMP-dependent Na+/H+ antiporter of the trout red blood cell (Borgese et al., 1986). If glutaraldehyde is added when the cells are activated by cAMP in a chloride-containing medium, the activity of the exchanger is no longer inhibited when Cl- is replaced by NO3-. Conversely, after fixation in NO3- medium replacement of NO3- by Cl- has very little stimulatory effect. This indicates that the anion dependence is not a specific requirement for the exchange process but that the anion environment is critical for the switching on of the Na+/H+ exchanger and for the maintenance of its activated configuration.

Animals↗

PubMed1989

Effect of catecholamines on deformability of red cells from trout: relative roles of cyclic AMP and cell volume.

1. In the presence of catecholamine the nucleated red blood cells of trout show a large increase in cell volume as a result of an accumulation of sodium and chloride due to activation of an amiloride-sensitive, cyclic AMP-dependent Na+-H+ exchanger allowing Na+ to enter in exchange for internal H+. 2. The activation of this cyclic AMP-dependent Na+-H+ exchange is considered to be involved in an adaptive response to hypoxia by increasing the oxygen-carrying capacity of erythrocytes. But cell swelling could increase resistance to blood flow and thus impair the expected physiological advantages for oxygen transport. The effect of catecholamine on the deformability properties of the red blood cells has been studied by measuring the rate at which blood flows through a Nucleopore filter (5 microM). 3. The results show that stimulation by catecholamine in fact increases the erythrocyte deformability, a response which must favour the supply of oxygen at the tissue level. 4. Hormonal stimulation increases the cellular cyclic AMP content (and cyclic AMP-dependent phosphorylation of cytoskeleton proteins could influence cell deformability) and the cell volume. It has been shown that when cellular cyclic AMP content is increased under conditions where the cell cannot swell, the erythrocyte becomes more rigid and not more deformable. Conversely the results show a systematic coincidence between cell swelling and deformability increase. The precise way in which volume change and deformability are interrelated needs more study.

Amiloride↗

PubMed1989

Na+-H+ exchange and pH regulation in red blood cells: role of uncatalyzed H2CO3 dehydration.

Erythrocytes of rainbow trout respond to adrenergic stimulation by activation of a Na+-H+ exchange. When red blood cells are suspended in their own plasma and equilibrated with a convenient gas mixture in a tonometer, the extrusion of H+ induces a fast, very strong acidification of the blood (by 0.5-0.7 pH units), explained as follows. Excretion of H+ into a medium containing HCO3- causes the formation of H2CO3. The uncatalyzed dehydration of H2CO3 is slow so that H+ accumulates above the level that would prevail at equilibrium, promoting a strong acid disequilibrium pH. Then the blood pH progressively returns to a value close to its initial value because of the slow uncatalyzed dehydration of H2CO3 and washout of the CO2 so produced. The period of acid disequilibrium pH, however, is lengthened because part of the CO2 generated by the spontaneous dehydration is not washed out by tonometry but diffuses into the red cells where it is rapidly converted into HCO3- and H+ by carbonic anhydrase and then excreted by Na+-H+ and Cl-HCO3- exchangers. This recycling process "refuels" the ionic reaction, increasing the time needed to reach equilibrium. The anion exchanger does not sense this strong acid disequilibrium pH, since the external HCO3- concentration is practically unchanged at that time. During the extracellular pH (pHe) recovery period, simultaneously extracellular HCO3- content decreases and intracellular Cl- content increases. Thus intracellular pH and pHe appear to be uncoupled. This overall interpretation is confirmed by experiments using carbonic anhydrase and drugs such as propranolol and amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

PubMed1988

Adaptive respiratory responses of trout to acute hypoxia. I. Effects of water ionic composition on blood acid-base status response and gill morphology.

The effects of various levels of hypoxia (PWO2 ranging from 10 to 60 Torr) on arterial blood gases (PaO2 and PaCO2) and acid-base status were investigated in trout at 15 degrees C. The hypoxic responses of two stocks of trout living in natural waters having very different levels of NaCl (1.0 mmol.L-1 and 0.1 mmol.L-1) and carbonate alkalinity (0.4 mmol.L-1 and 2.4 mmol.L-1) were compared. The use of an extracorporeal circulation method made it possible to continuously monitor the pH changes. The different patterns of the acid-base status observed in response to hypoxia depend on the evolution of PaO2. Two critical PaO2 thresholds were defined. Crossing the upper (about 15 Torr) induces metabolic acidosis which is normally followed by pH recovery, while crossing the lower (about 10 Torr) promotes loss of capacity to compensate acidosis. The NaCl concentration of the water drastically modifies the fish sensitivity to hypoxia: fish living in water with a low NaCl concentration have less resistance to hypoxic exposure. This may be explained by the fact that in fish living in low NaCl concentrations, the secondary gill lamellae are surrounded by chloride cells, which considerably reduce the surface area available for gas exchange. Consequently a modest fall in PWO2 induces a drastic reduction of the arterial oxygen tension which crosses the lower critical PaO2 threshold.

Acid-Base Equilibrium↗

PubMed1988

Adaptive respiratory responses of trout to acute hypoxia. II. Blood oxygen carrying properties during hypoxia.

The effects of deep and acute hypoxia (PwO2 = 25 Torr) on oxygen transport characteristics (Hill number (n) and P50) were investigated in trout at 15 degrees C. When a fish is submitted to such an acute and deep hypoxia, a metabolic acidosis develops as soon as the arterial oxygen tension drops to about 15 Torr. We first showed that the hemoglobin of blood sampled at the end of the acidification period has an increased oxygen affinity. This improved affinity could be explained by the internal alkalisation of erythrocytes due to the extrusion of protons via a beta-adrenergic stimulation of Na+/H+ exchanges occurring at the onset of hypoxia and responsible for extracellular acidosis. Secondly we observed a significant increase (about 20%) of the number of blood cells per volume of blood during the acidosis. This cell number stays constant afterwards. The dual effects of a higher hemoglobin oxygen affinity and a greater amount of available hemoglobin improving blood oxygen loading at the fish gills appear to be a fast adaptive response to acute hypoxia. Surprisingly, we found that the elevated affinity occurring during acidosis remained constant as long as the fish were maintained in hypoxia, in spite of possible large variations of extracellular pH (pHe). This result is difficult to reconcile with the idea that the increase in affinity is imposed by intracellular pH (pHi), since in red blood cells pHi depends on pHe, thus any modification of pHe would in this case modify oxygen affinity.

Animals↗

PubMed1988

Adaptive respiratory responses of trout to acute hypoxia. III. Ion movements and pH changes in the red blood cell.

In the preceding paper acute hypoxia was shown to elicit within minutes an increase in the blood O2 affinity. From the present data it appears that this rapid change in blood P50 value can be ascribed to an important alkalization of the red blood cell despite a simultaneous decrease in extracellular pH (pHe). The intracellular alkalization is only partially due to beta-adrenergic stimulation of Na/H exchange, deoxygenation of hemoglobin and the rapid decrease of PaCO2 due to hyperventilation being involved in this process via the chloride shift. This high value of intraerythrocytic pH (pHi) is then maintained practically constant throughout the time the fish is kept in hypoxia despite wide changes of external pH. The blocking of pHi accounted for the constant O2 content observed during hypoxia. The uncoupling of pHi from pHe, which occurs at the onset of hypoxia, is still unexplained: for instance, it is not due to inhibition of the anion exchanger responsible for the passive distribution of H+ across the red cell membrane. A general scheme of all the mechanisms involved in the emergency adaptive response to acute hypoxia is presented.

Animals↗

PubMed1988

Desensitization by external Na of the cyclic AMP-dependent Na+/H+ antiporter in trout red blood cells.

The erythrocytes of the trout, Salmo gairdneri, react to beta-adrenergic stimulation by activating a cyclic AMP-dependent and amiloride-sensitive Na+/H+ antiporter (see Borgese, F., F. Garcia-Romeu, and R. Motais, Journal of General Physiology, 1986, 87:551-566). The present study traces the kinetic behavior of the unidirectional Na fluxes after stimulation by isoproterenol. A very considerable increase (100-fold) of the unidirectional Na influx (JNa(in)) follows the addition of isoproterenol to the erythrocyte suspension. After 1.5 min, JNa(in) falls suddenly, and asymptotically diminishes toward the nonstimulated flux level. The unidirectional Na efflux (JNa(out)) proceeds according to similar kinetics. The decrease of JNa(in) and JNa(out)is not linked to either a change in the driving forces of the transported ions or a decrease of the cyclic AMP concentration but to a desensitization of the Na+/H+ antiporter. This desensitization is dependent on the external Na concentration and is not controlled by internal Na, cell swelling, or external Ca.

Absorption↗

PubMed1987

The control of Na+/H+ exchange by molecular oxygen in trout erythrocytes. A possible role of hemoglobin as a transducer.

It has previously been shown that addition of catecholamines to a suspension of trout erythrocytes induces an enlargement of the cells owing to an uptake of NaCl mediated by a cAMP-dependent, amiloride-sensitive Na+/H+ exchange. In this article, we show that the change in cell volume induced by catecholamines is much greater when the erythrocytes are incubated in N2 than when they are in O2. This difference is explained by an inhibition of the cAMP-dependent Na+/H+ exchange by O2. The inhibition is not reversed in cells incubated in O2 but poisoned with cyanide. It cannot be explained by a difference in the content of cAMP in O2 and in N2. In a CO atmosphere, in which the cells are anoxic, swelling and Na permeability are not increased as they are in N2: in CO, the cells behave as they do in O2. Moreover, cells previously exposed to CO and then put in an N2 atmosphere do not show the expected increase in Na+/H+ exchange. This strongly indicates that the binding of CO to hemoglobin, which persists during the subsequent exposure to N2, is the primary event responsible for the inhibition. As CO substitutes for O2 in binding to hemoglobin, the effect of O2 in the control of Na+/H+ exchange is probably explained by this interaction with heme. (Allen and McManus [1968. Biophysical Journal. 8:125a] previously described a similar effect of CO on passive Na permeability in duck red cells.) It is proposed that the hemoglobin, by interacting differently, according to its degree of oxygenation, with the cytoplasmic segment of band 3 protein, may influence some transport function, such as Na+/H+ exchange. The physiological significance of a control of Na+/H+ exchange by molecular O2 is discussed.

Animals↗

PubMed1987

Control of cell volume and ion transport by beta-adrenergic catecholamines in erythrocytes of rainbow trout, Salmo gairdneri.

1. Trout red cells suspended in an isotonic medium containing beta-adrenergic catecholamines or adenosine 3',5'-phosphate (cyclic AMP) enlarge rapidly to reach a new steady-state volume which is maintained as long as hormone is present. The volume response is not changed by inhibition of the Na+-K+ pump with ouabain. The new steady-state volume was shown to result from a dynamic equilibrium involving the simultaneous functioning of two regulatory processes induced by hormone: a volume increase response that causes cells to enlarge by gaining Na+ and a volume decrease response that causes cells to shrink by losing K+. 2. As previously described, the volume increase response due to NaCl entry, is mediated by the activation by cyclic AMP of a Na+-H+ antiport operating in parallel to Cl(-)-OH- exchanges. In addition, it is shown in this paper that the Na+ uptake is a discontinuous, oscillatory process and that NaCl entry continues for several hours, i.e. as long as hormone is present. 3. The volume decrease response involves a passive, Cl(-)-dependent K+ loss. Na+ cannot use this pathway. The response is blocked by replacement of Cl- by NO3-, by loop diuretics (furosemide, bumetanide) but also by inhibitors of the anion exchanger (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), niflumic acid). The activation of this ouabain-insensitive, Cl(-)-dependent K+ transport system is not directly triggered by cyclic AMP. It involves an all-or-none type of switching phenomenon which occurs when the cells swell to a certain volume. Thus it is a regulatory response to the increase in cell volume induced by stimulation of the Na+-H+ exchange by cyclic AMP. Inactivation is also volume dependent: when the cell size approaches the initial size the pathway shuts off. Thus the controlling mechanism of the K+ pathway acts like a reversible on-off switch that operates around a given volume. Ca2+ was not found to be involved in this control. Cyclic AMP is not necessary to keep the activated K+ pathway open but it could be one of the factors involved in the activating process. 4. There are several lines of evidence indicating that in trout red cells the volume decrease and the volume increase responses may not be brought about by the same transport mechanism operating in different modes. The movements of Na+, K+ and Cl- account for the water movements during volume increase and decrease. Thus movements of other solutes such as amino acids need not be considered.

Amiloride↗

PubMed1987

Ion movements and volume changes induced by catecholamines in erythrocytes of rainbow trout: effect of pH.

1. Trout red cells suspended in an isotonic medium containing catecholamines or adenosine 3',5'-phosphate (cyclic AMP) enlarge rapidly to reach a new steady-state volume which is maintained as long as hormone is present. 2. The present investigation demonstrates that the maximum swelling reached by the cells is strongly pH dependent. At pH 7.55 the cells enlarge more rapidly than at pH 7.95 and they reach a maximal volume which is much greater. It is explained by a differential effect of pH on two pathways controlling the movements of cations: K+ loss decreases as pH becomes more acidic in a roughly linear manner. On the contrary Na+ uptake increases as pH becomes more acidic with a maximum around pH 7.30 and then decreases. From this pH dependence it can be expected that the maximum enlargement occurs at about pH 7.30. 3. The complex relationship describing the change in the activity of the Na+-H+ exchanger as a function of pH (bell-shaped curve) is explained by the predominant influence of internal H+ on the antiporter in the alkaline range of pH and by the predominant influence of external H+ on the transporter in the acidic range.

Animals↗

PubMed1987

Role of adrenergic-dependent H+ release from red cells in acidosis induced by hypoxia in trout.

The response to severe hypoxia is characterized in trout by a sudden drop in blood pH, which is of metabolic origin, and by an increase in the blood concentration of adrenaline. This acidification is biphasic in nature. The first phase of acidification is not associated with a rise in the blood lactate concentration and no longer occurs after pretreatment of the fish with a beta-blocker agent, propranolol. Thus an acid other than lactic acid is released into the blood at the onset of hypoxia and this release, which is under beta-adrenergic control, is responsible for the first phase of acidification. On the other hand the second phase of acidification is related to an increase in blood lactate and is not modified by a beta-blocker agent. We have also demonstrated that deep hypoxia promotes a rapid increase in red blood cell volume and that this cell enlargement is coincident with a large net uptake of Na+ and Cl-. In the presence of beta-blocking agents the Na+ uptake is blocked and the swelling of the cells is considerably inhibited. The residual swelling is clearly due to the chloride shift induced by both deoxygenation of hemoglobin and change in blood pH. In the light of data obtained in vitro on the effect of catecholamines on trout erythrocytes, it can be considered that the first phase of acidification occurring at the onset of hypoxia, and that is under beta-adrenergic control, is due essentially to the release of H+ by red blood cells in exchange with external sodium mediated by a beta-adrenergic-stimulated Na+-H+ exchanger.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗