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Activity of the sympathetic-adrenomedullary system in rats after space flight on the COSMOS biosatellites
87192. Adv. Space Res. Vol.1, pp.l ©COSPAR, 1981. Printed in Great Britain.
0273_1177181/04010187$05.00/0
AS RELATED TO STRESS
ACTIVITY OF THE SYMPATHETICADRENOMEDULLARY SYSTEM IN RATS AFTER SPACE FLIGHT ON THE COSMOS BIOSATELLITES R. KvethanskS’, M. Viga~, R.A. Tigranyan,’ Németh and L. Macho ~.
Institute ofExperimental Endocrinology, Centre of Physiological Sciences, Slovak Academy of Sciences, Brati~lava,Czechoslovakia ‘Institute ofMedicobiological Problems, Moscow, USSR ABSTRACT The indicators of adrenomedullary activity (catecholamine content (CA) and the activity of the catecholamine—synthesizing enzymes tyrosine hydroxylase (TN) and dopamine—~—hydroxy1ase(DBH)) were measured in the adrenal glands of rats living in a state of weightlessness for 18.5—19.5 days on board the biosateilites COSMOS 936 and COSMOS 1129 None of these indicators was significantly changed by space flight, neither in the group living in a state of weightlessness nor in the group living in a centrifuge on board the spacecraft and exposed to artificial gravity of 1 g (COSMOS 936) Animals exposed after space flight to repeated immobilization stress on Earth showed a significant decrease of adrenal adrenaline and an~appreciable increase in adrenal TN activity compared to stressed animals which were not in space. These results suggest that a prolonged state of weightlessness during space flight does not by itself represent an intensive stressful stimulus for the adrenomedullary system but potentiates the response of cosnionauts to stress after return to Earth. INTRODUcTION The state of weightlessness, which is a very nonphysiological situation for both humans and animals, has become a major medical problem during prolonged space flights (1). Is the state of weightlessness a stressful stimulus for the mammalian organisms? If so, is adaptation of the organism to this situation possible? Activation of the adrenal medulla, resulting in secretion of CA, is one of the classical indicators of a stress reaction. Published data as well as our own results demonstrate that an intensive acute stressful stimulus induces a significant decrease of adrenal adrenaline (ADR) in rats under normal conditions of gravity on Earth (2) An intensive stressful stimulus applied repeatedly or chronically, however, has an opposite effect increase of adrenal CA content (2) together with increased CA biosynthesis (3) and elevated activity of the CA—synthesizing enzymes TN and phenylethanolamine N—methyl transferase (PNMT) (4) as well as DBR (5) The question whether the state of weightlessness has a stressful influence on the activity of the sympathetic—adrenomedullary system (SAS) was studied in rats which experienced space flight on the COSMOS biosatellites The results obtained from COSMOS 782 have already been published (6,7,8). These results indicated that SAS was not significantly activated by the 20—day space flight, yet they did not answer the question whether a prolonged state of weightlessness acted as an intensive 187
188
N. Kvet~ansk~et al.
stressor. This was to be answered by analyzing the material from the biosatellites COSMOS 936 and COSMOS 1129. On board the biosatellite COSMOS 936, some rats were caged in a centrifuge (1 g) to distinguish the effect of weightlessness from other stressful factors connected with space flight. The experiment on COSMOS 1129 was based on our previous results obtained in rats exposed to single or repeated immobilization stress on Earth (2,3, 4,5). On the basis of our experience in the field of stress we argued that if rats are chronically exposed to intensive stressors during space flight, after return to Earth, they should react to repeated immobilization stress as chronically stressed rats. If however, space flight does not induce prolonged intensive stressful stimulation of SAS, then the rats should react to immobilization stress as animals exposed to stress for the first time. Thus, the goal of the present work was to measure adrenal catecholamines and their synthesizing enzymes in rats after space flight on the biosatellites COSMOS 936 and COSMOS 1129 and to evaluate the possible stressful effect of prolonged weightlessness on the activity of the sympathetic—adrenomedullary system. MATERIALS AMD METHODS The experiments were performed on male Wistar rats (SPF colony, Bratislava) weighing 200—250 g. The rats from COSMOS 936 were decapitated in two groups: either 6—10 hours or 25 days after the 19.5—day—long space flight. Aboard the biosatellite, the rats were kept in individual cages in a state of weightlessness (W) or in the centrifuge (W+C) in which an artificial gravitational force of 1 g acted during almost the whole flight. During the touchdown manoeuvre the centrifuge was switched off because of technical reasons. The results obtained were compared with the control group (Cc) and with a synchronous group which was exposed on Earth to similar conditions as group W in space except for the state of weightlessness. Another ground control group was centrifuged without simulation of the other flight conditions (CGR). The experiments on COSMOS 1129 were done in a spacecraft environment similar to those from COSMOS 936, but there was no centrifuge on board COSMOS 1129 a~dthe biosatellite spent only 18.5 days in space. The animals were decapitated in two groups: immediately after landing (7—lohrs), and 6 days after landing. A third group was exposed after landing to immobilization Stress 5 times, daily for 150 minutes (2,4), and the animals were killed immediately after the last exposure. The first immobilization was performed directly at the landing site but the following day (during transportation of the rats to Moscow) this procedure was omitted. The control and synchronous groups were also exposed to repeated immobilization stress. Adrenal CA were measured by the fluorometric method (9) and the activity of TN (10) and DBH (11) by using radiolabelled substrates. Results are expressed as means ±SEM and statistical significance was calculated by Student’s t—test. RESULTS COSMOS 936. Adrenal adrenaline (Pig.l.) and noradrenalime content in rats of the flight group which were living in a state of weightlessness (W) and also in the group which was centrifuged during flight (W + C), was not significantly changed compared to the control or synchronous groups. Twenty—five days after landing there were no significant changes in the adrenal adrenaline levels. Adrenal TH activity (Fig.2.) and adrenal DBH activity (Fig.3.) were not significantly changed in the flight groups compared to control groups. The only significant rise of DBH was found in the CGR group, killed 25 days after landing.
The Rat SympatheticAdtenomedullary System after Space Flight
—
U
e 10
CC
W
~
SYNCHRONOUS
V/A
FLIGHT
W~C CGRECG
6HRS
W
189
J
W.C CGR
ZSDAYS LANDING
AFTER
Fig.l. Adrenaline content in the adrenal glands of rats after space flight on COSMOS 936. CC — ground control, W— flight in weightlessness, W + C — flight in centrifuge, CGR — centrifuged ground control without flight simulation. Synchronous groups were studied on Earth with animals kept in similar cages as aboard or in the centrifuge and with simulation of some flight parameters such as take—off and landing. Mean ±SEM of 5 animals. COSMOS 1129. Table 1 shows that neither adrenal ADR nor adrenal TN activity were changed in rats killed immediately after landing in comparison with the control and synchronous group. Six days after landing these indicators remained unchanged compared to. the control group but were somewhat higher compared to the synchronous group. However in the rats that were exposed 5 times to forced immobilization, during the 6 days after space flight, the adrenal ADR content was significantly decreased and the adrenal TN activity was increased compared to the control and synchronous repeatedly immobilized groups (Table 1).
~3O~
ri CC
~
j
~
W
W~C CGR
6HRS AFTER
I
FLIGHT
~
CC
W
W~CCGR
25 DAYS LANDING
see Fig.l).
190
R 180-
110 60.
r
Kvetj~iabsk~ et al
~SYNCHRONOlJS
P77] FLIGHT Fig.3.
I
~ ....L
CC
W 6 HRS
wC
CGR
CC
~
~ ~ ~ CG~
after space flight on COSMOS 936 (for explanation of symbols
LANDING
Group
Adrenaline
TN
(nmol/adrenal)
(nmol h~/adrenal)
±11.8
40.3
125.2
2.0
36.5
147.7
12.1
31.5
±3.1 ±3.2 ±1.4
±18.3 ± 61a
39.6
±1.9
~
87.8
± 8.5
32.5
±3~a ±2.0
Control
88.5
3.9
66.6
3.5
Flight Synchronous
55.6 ~ 54a,c 84.8 ±10.1
104.1 71.4
±44b,c ±5.6
Control
137.2
7 hours
Flight
(n
Synchronous
Control
115.2
6 days
Flight
111.9
(n
Synchronous
6 days 5xDQ~OBIL.d (n =
=
hydroxylase activity in rats
Effect of Space Flight on COSMOS 1129 upon the Parameters of Adrenomedullary Activity
Time after flight
=
~“
25 DAYS AFTER
TABLE 1.
i
Adrenal dopamine-~—
7)
6)
dAnimals were exposed to immobilization stress for 150
mm.
daily
and killed
a~ter
the last interval still mounted on the board. For details see METHODS. Mean SEN of 6—7 rats. Statistical significance: a, p
—
DISCUSSION The measured indicators of SAS in rats,~adrenal catecholamines and their synthesizing enzymes, had only been studied in one prior space experiment on the biosatellite COSMOS 782 The results of the latter flight showed that the activity of the adrenal medulla was not significantly changed after the 20 days in a state of weightlessness in space (7 8) A small elevation of TN was observed, which suggested that the rats were, at least for a short period, exposed to some stressor. On the basis of the results obtained from COSMOS 782, it was impossible to say whether the TH change was induced by the state of weightlessness or by some stressors connected with landing or with manipulations on Earth after landing. This question was to be answered by the experiment on COSMOS 936 with the most
The Rat sympathetic—Adrenomedullary System after Space Flight
191
adequate control group (animals centrifuged during flight) and by the experiment on COSMOS 1129, in which the rats after return to Earth were exposed to repeated immobilization stress In both these experiments the content of adrenal adrenaline and adrenal TN activity (Figs 1, 2 and Table 1) were not changed in the rats decapitated immediately after landing suggesting that most probably the activity of SAS was not influenced during space flight by any chronic stressor The activity of adrenal TN is a sensitive indicator of long—duration stress, which has been demonstrated by a several fold increase of TN after repeated or chronic exposure of rats to different stressors (4,12,13,14,15). Repeated forced immobilization is responsible for a 3 to 4—fold elevation of adrenal TN and DBH activity in rats (4,5). On the other hand a 3—week stay of rats in space failed to affect TN activity in the adrenals of flight rats both from COSMOS 936 and 1129. One might speculate that during the early portion of space flight in weightlessness the activity of TN and DBH were actually elevated but that in the later periods of the space flight an adaptive mechanism could have been called into play, resulting in a gradual return of TN to control values. This possibility, however, is not likely, because the increased TN activity induced by 7—times repeated immobilization returns to control values only after 14 days, with a half—life of 3 days (4). The same half—life for the return of chronic cold—induced TN activity increase has been reported by Chuang et al. (16). It should be noted that in COSMOS 936, adrenal CA and enzymes displayed similar values in the group under weightlessness and in the centrifuged group under weightlessness. As the state of weightlessness did not induce any changes in SAS, no correction could be effected by the on board artificial gravitation of 1 g produced by centrifugation These findings indicate that during space flight any other long—acting intensive stressor can be excluded as far as the SAS activation is concerned. The results from COSMOS 1129 (Table 1), however, clearly demonstrate that rats, which after 18.5 days of space flight were exposed to stress on Earth, shoved a significantly increased adrenomedullary activity compared to the control and synchronous groups. The results from COSMOS 1129, interpreted in the light of our previous findings in immobilized rats (2,3, 4,5), indicate that during space flight no intensive long—acting stressor could have affected the SAS activity. The fact that after return to Earth, the animals responded to stress more intensively suggests that during space flight some factor (maybe weightlessness) must have been effective in sensitizing SAS to an enhanced response to intensive stress. This might have been brought about by diminished need, due to the state of weightlessness during space flight, of the organism for the activity of SAS. Our finding of a pronounced reaction of rats to stress after prolonged space flight is a physiological phenomenon which should be considered, particularly with reference to the readaptation after space flight. REFERENCES I.
O.G. Gazenko, A.M. Genin, E.A. lijin, L.V. Serova, R.A. Tigranjan and V S Oganov, Izvestija AN SSSR, Seri3a Biologi~eskaja No !~5 (1980) (in Russian).
2.
R. Kvet~iansk~ and L. Mikula~,Endocrinology 87, 738 (1970).
3.~
R. Kveti~anskf,V.K. Weise, G.P. Gewirtz and i.j. Kopin, Endocrinolo~y89, 46 (1971).
4.
R. KvetI~ansk~,V.K. Weise and I.J.
5.
R. Kvetfiansk~, G.P. Gewirtz, V.K. Weise and I.J. 81 (1971).
Kopin, Endocrinology
87, 744 (1970).
Kopin, Mol. Pharmacol.
7,
192
R. Kvet~ansk~ et al.
6.
A.M. Genin, in: Effect of Dynamic Factors of ~p~c!f]4g~ Organism of Animals, Nauka, Moscow, 1979 (in Russian).
7.
R. Kveti’iansk3i, R.A. Tigranjan, T. Torda, U. Rep~eková,E. Jahnovg and K. Murga~,Kosm es~j~BiologijaMedicina 14, No 1, 24 (in Russian) (1980).
8.
R. Kveticansk~,R.A. Tigranjan, T. Torda, U. Rep~ekovg,E. Jahnová and K. Murga~, in: Effect of ~ynamic Factors Spacef light on the 61 of(in Russian). Organism of Animals, Nauk~, Moscow, 1979, p.
9.
U.S.v. Euler and F. Lishajko, Acta Physiol. Scand, 51, 348 (1961).
10.
T. Nagatsu, N. Lewitt and S. Udenfriend, Analyt, Biochem. 9, 122 (1964),
11,
P.B. Molinoff, R. Weinshilboum and J. Axeirod, J. Pharmacol. ~ 178, 425 (1971).
12.
3. Axelrod, R.A. Mueller, J.P. Henry, P.M. Stephens, Nature, Lond. 225, 1059 (1970).
13.
B.D. Chagat and S. Horenstein, in: Catecholamines and Stress, Pergamon Press, Oxford 1976, p.257.
14.
R. Kvet?ianskj, G.P. Gewirtz, V.K. Weise and 1.3. Kopin, Amer. 3. Physiol. 220, 928 (1971).
15.
R. Kvet~anskj, in: Frontiers in Catecholamine Research, Pergamon Press, Oxford, 1973, p.223.
16,
D. Chuang, C. Zsilla
and E. Costa, Mol. Pharmacol.
on the
11, 784 (1975).
Ther.
0273_1177181/04010187$05.00/0
AS RELATED TO STRESS
ACTIVITY OF THE SYMPATHETICADRENOMEDULLARY SYSTEM IN RATS AFTER SPACE FLIGHT ON THE COSMOS BIOSATELLITES R. KvethanskS’, M. Viga~, R.A. Tigranyan,’ Németh and L. Macho ~.
Institute ofExperimental Endocrinology, Centre of Physiological Sciences, Slovak Academy of Sciences, Brati~lava,Czechoslovakia ‘Institute ofMedicobiological Problems, Moscow, USSR ABSTRACT The indicators of adrenomedullary activity (catecholamine content (CA) and the activity of the catecholamine—synthesizing enzymes tyrosine hydroxylase (TN) and dopamine—~—hydroxy1ase(DBH)) were measured in the adrenal glands of rats living in a state of weightlessness for 18.5—19.5 days on board the biosateilites COSMOS 936 and COSMOS 1129 None of these indicators was significantly changed by space flight, neither in the group living in a state of weightlessness nor in the group living in a centrifuge on board the spacecraft and exposed to artificial gravity of 1 g (COSMOS 936) Animals exposed after space flight to repeated immobilization stress on Earth showed a significant decrease of adrenal adrenaline and an~appreciable increase in adrenal TN activity compared to stressed animals which were not in space. These results suggest that a prolonged state of weightlessness during space flight does not by itself represent an intensive stressful stimulus for the adrenomedullary system but potentiates the response of cosnionauts to stress after return to Earth. INTRODUcTION The state of weightlessness, which is a very nonphysiological situation for both humans and animals, has become a major medical problem during prolonged space flights (1). Is the state of weightlessness a stressful stimulus for the mammalian organisms? If so, is adaptation of the organism to this situation possible? Activation of the adrenal medulla, resulting in secretion of CA, is one of the classical indicators of a stress reaction. Published data as well as our own results demonstrate that an intensive acute stressful stimulus induces a significant decrease of adrenal adrenaline (ADR) in rats under normal conditions of gravity on Earth (2) An intensive stressful stimulus applied repeatedly or chronically, however, has an opposite effect increase of adrenal CA content (2) together with increased CA biosynthesis (3) and elevated activity of the CA—synthesizing enzymes TN and phenylethanolamine N—methyl transferase (PNMT) (4) as well as DBR (5) The question whether the state of weightlessness has a stressful influence on the activity of the sympathetic—adrenomedullary system (SAS) was studied in rats which experienced space flight on the COSMOS biosatellites The results obtained from COSMOS 782 have already been published (6,7,8). These results indicated that SAS was not significantly activated by the 20—day space flight, yet they did not answer the question whether a prolonged state of weightlessness acted as an intensive 187
188
N. Kvet~ansk~et al.
stressor. This was to be answered by analyzing the material from the biosatellites COSMOS 936 and COSMOS 1129. On board the biosatellite COSMOS 936, some rats were caged in a centrifuge (1 g) to distinguish the effect of weightlessness from other stressful factors connected with space flight. The experiment on COSMOS 1129 was based on our previous results obtained in rats exposed to single or repeated immobilization stress on Earth (2,3, 4,5). On the basis of our experience in the field of stress we argued that if rats are chronically exposed to intensive stressors during space flight, after return to Earth, they should react to repeated immobilization stress as chronically stressed rats. If however, space flight does not induce prolonged intensive stressful stimulation of SAS, then the rats should react to immobilization stress as animals exposed to stress for the first time. Thus, the goal of the present work was to measure adrenal catecholamines and their synthesizing enzymes in rats after space flight on the biosatellites COSMOS 936 and COSMOS 1129 and to evaluate the possible stressful effect of prolonged weightlessness on the activity of the sympathetic—adrenomedullary system. MATERIALS AMD METHODS The experiments were performed on male Wistar rats (SPF colony, Bratislava) weighing 200—250 g. The rats from COSMOS 936 were decapitated in two groups: either 6—10 hours or 25 days after the 19.5—day—long space flight. Aboard the biosatellite, the rats were kept in individual cages in a state of weightlessness (W) or in the centrifuge (W+C) in which an artificial gravitational force of 1 g acted during almost the whole flight. During the touchdown manoeuvre the centrifuge was switched off because of technical reasons. The results obtained were compared with the control group (Cc) and with a synchronous group which was exposed on Earth to similar conditions as group W in space except for the state of weightlessness. Another ground control group was centrifuged without simulation of the other flight conditions (CGR). The experiments on COSMOS 1129 were done in a spacecraft environment similar to those from COSMOS 936, but there was no centrifuge on board COSMOS 1129 a~dthe biosatellite spent only 18.5 days in space. The animals were decapitated in two groups: immediately after landing (7—lohrs), and 6 days after landing. A third group was exposed after landing to immobilization Stress 5 times, daily for 150 minutes (2,4), and the animals were killed immediately after the last exposure. The first immobilization was performed directly at the landing site but the following day (during transportation of the rats to Moscow) this procedure was omitted. The control and synchronous groups were also exposed to repeated immobilization stress. Adrenal CA were measured by the fluorometric method (9) and the activity of TN (10) and DBH (11) by using radiolabelled substrates. Results are expressed as means ±SEM and statistical significance was calculated by Student’s t—test. RESULTS COSMOS 936. Adrenal adrenaline (Pig.l.) and noradrenalime content in rats of the flight group which were living in a state of weightlessness (W) and also in the group which was centrifuged during flight (W + C), was not significantly changed compared to the control or synchronous groups. Twenty—five days after landing there were no significant changes in the adrenal adrenaline levels. Adrenal TH activity (Fig.2.) and adrenal DBH activity (Fig.3.) were not significantly changed in the flight groups compared to control groups. The only significant rise of DBH was found in the CGR group, killed 25 days after landing.
The Rat SympatheticAdtenomedullary System after Space Flight
—
U
e 10
CC
W
~
SYNCHRONOUS
V/A
FLIGHT
W~C CGRECG
6HRS
W
189
J
W.C CGR
ZSDAYS LANDING
AFTER
Fig.l. Adrenaline content in the adrenal glands of rats after space flight on COSMOS 936. CC — ground control, W— flight in weightlessness, W + C — flight in centrifuge, CGR — centrifuged ground control without flight simulation. Synchronous groups were studied on Earth with animals kept in similar cages as aboard or in the centrifuge and with simulation of some flight parameters such as take—off and landing. Mean ±SEM of 5 animals. COSMOS 1129. Table 1 shows that neither adrenal ADR nor adrenal TN activity were changed in rats killed immediately after landing in comparison with the control and synchronous group. Six days after landing these indicators remained unchanged compared to. the control group but were somewhat higher compared to the synchronous group. However in the rats that were exposed 5 times to forced immobilization, during the 6 days after space flight, the adrenal ADR content was significantly decreased and the adrenal TN activity was increased compared to the control and synchronous repeatedly immobilized groups (Table 1).
~3O~
ri CC
~
j
~
W
W~C CGR
6HRS AFTER
I
FLIGHT
~
CC
W
W~CCGR
25 DAYS LANDING
see Fig.l).
190
R 180-
110 60.
r
Kvetj~iabsk~ et al
~SYNCHRONOlJS
P77] FLIGHT Fig.3.
I
~ ....L
CC
W 6 HRS
wC
CGR
CC
~
~ ~ ~ CG~
after space flight on COSMOS 936 (for explanation of symbols
LANDING
Group
Adrenaline
TN
(nmol/adrenal)
(nmol h~/adrenal)
±11.8
40.3
125.2
2.0
36.5
147.7
12.1
31.5
±3.1 ±3.2 ±1.4
±18.3 ± 61a
39.6
±1.9
~
87.8
± 8.5
32.5
±3~a ±2.0
Control
88.5
3.9
66.6
3.5
Flight Synchronous
55.6 ~ 54a,c 84.8 ±10.1
104.1 71.4
±44b,c ±5.6
Control
137.2
7 hours
Flight
(n
Synchronous
Control
115.2
6 days
Flight
111.9
(n
Synchronous
6 days 5xDQ~OBIL.d (n =
=
hydroxylase activity in rats
Effect of Space Flight on COSMOS 1129 upon the Parameters of Adrenomedullary Activity
Time after flight
=
~“
25 DAYS AFTER
TABLE 1.
i
Adrenal dopamine-~—
7)
6)
dAnimals were exposed to immobilization stress for 150
mm.
daily
and killed
a~ter
the last interval still mounted on the board. For details see METHODS. Mean SEN of 6—7 rats. Statistical significance: a, p
—
DISCUSSION The measured indicators of SAS in rats,~adrenal catecholamines and their synthesizing enzymes, had only been studied in one prior space experiment on the biosatellite COSMOS 782 The results of the latter flight showed that the activity of the adrenal medulla was not significantly changed after the 20 days in a state of weightlessness in space (7 8) A small elevation of TN was observed, which suggested that the rats were, at least for a short period, exposed to some stressor. On the basis of the results obtained from COSMOS 782, it was impossible to say whether the TH change was induced by the state of weightlessness or by some stressors connected with landing or with manipulations on Earth after landing. This question was to be answered by the experiment on COSMOS 936 with the most
The Rat sympathetic—Adrenomedullary System after Space Flight
191
adequate control group (animals centrifuged during flight) and by the experiment on COSMOS 1129, in which the rats after return to Earth were exposed to repeated immobilization stress In both these experiments the content of adrenal adrenaline and adrenal TN activity (Figs 1, 2 and Table 1) were not changed in the rats decapitated immediately after landing suggesting that most probably the activity of SAS was not influenced during space flight by any chronic stressor The activity of adrenal TN is a sensitive indicator of long—duration stress, which has been demonstrated by a several fold increase of TN after repeated or chronic exposure of rats to different stressors (4,12,13,14,15). Repeated forced immobilization is responsible for a 3 to 4—fold elevation of adrenal TN and DBH activity in rats (4,5). On the other hand a 3—week stay of rats in space failed to affect TN activity in the adrenals of flight rats both from COSMOS 936 and 1129. One might speculate that during the early portion of space flight in weightlessness the activity of TN and DBH were actually elevated but that in the later periods of the space flight an adaptive mechanism could have been called into play, resulting in a gradual return of TN to control values. This possibility, however, is not likely, because the increased TN activity induced by 7—times repeated immobilization returns to control values only after 14 days, with a half—life of 3 days (4). The same half—life for the return of chronic cold—induced TN activity increase has been reported by Chuang et al. (16). It should be noted that in COSMOS 936, adrenal CA and enzymes displayed similar values in the group under weightlessness and in the centrifuged group under weightlessness. As the state of weightlessness did not induce any changes in SAS, no correction could be effected by the on board artificial gravitation of 1 g produced by centrifugation These findings indicate that during space flight any other long—acting intensive stressor can be excluded as far as the SAS activation is concerned. The results from COSMOS 1129 (Table 1), however, clearly demonstrate that rats, which after 18.5 days of space flight were exposed to stress on Earth, shoved a significantly increased adrenomedullary activity compared to the control and synchronous groups. The results from COSMOS 1129, interpreted in the light of our previous findings in immobilized rats (2,3, 4,5), indicate that during space flight no intensive long—acting stressor could have affected the SAS activity. The fact that after return to Earth, the animals responded to stress more intensively suggests that during space flight some factor (maybe weightlessness) must have been effective in sensitizing SAS to an enhanced response to intensive stress. This might have been brought about by diminished need, due to the state of weightlessness during space flight, of the organism for the activity of SAS. Our finding of a pronounced reaction of rats to stress after prolonged space flight is a physiological phenomenon which should be considered, particularly with reference to the readaptation after space flight. REFERENCES I.
O.G. Gazenko, A.M. Genin, E.A. lijin, L.V. Serova, R.A. Tigranjan and V S Oganov, Izvestija AN SSSR, Seri3a Biologi~eskaja No !~5 (1980) (in Russian).
2.
R. Kvet~iansk~ and L. Mikula~,Endocrinology 87, 738 (1970).
3.~
R. Kveti~anskf,V.K. Weise, G.P. Gewirtz and i.j. Kopin, Endocrinolo~y89, 46 (1971).
4.
R. KvetI~ansk~,V.K. Weise and I.J.
5.
R. Kvetfiansk~, G.P. Gewirtz, V.K. Weise and I.J. 81 (1971).
Kopin, Endocrinology
87, 744 (1970).
Kopin, Mol. Pharmacol.
7,
192
R. Kvet~ansk~ et al.
6.
A.M. Genin, in: Effect of Dynamic Factors of ~p~c!f]4g~ Organism of Animals, Nauka, Moscow, 1979 (in Russian).
7.
R. Kveti’iansk3i, R.A. Tigranjan, T. Torda, U. Rep~eková,E. Jahnovg and K. Murga~,Kosm es~j~BiologijaMedicina 14, No 1, 24 (in Russian) (1980).
8.
R. Kveticansk~,R.A. Tigranjan, T. Torda, U. Rep~ekovg,E. Jahnová and K. Murga~, in: Effect of ~ynamic Factors Spacef light on the 61 of(in Russian). Organism of Animals, Nauk~, Moscow, 1979, p.
9.
U.S.v. Euler and F. Lishajko, Acta Physiol. Scand, 51, 348 (1961).
10.
T. Nagatsu, N. Lewitt and S. Udenfriend, Analyt, Biochem. 9, 122 (1964),
11,
P.B. Molinoff, R. Weinshilboum and J. Axeirod, J. Pharmacol. ~ 178, 425 (1971).
12.
3. Axelrod, R.A. Mueller, J.P. Henry, P.M. Stephens, Nature, Lond. 225, 1059 (1970).
13.
B.D. Chagat and S. Horenstein, in: Catecholamines and Stress, Pergamon Press, Oxford 1976, p.257.
14.
R. Kvet?ianskj, G.P. Gewirtz, V.K. Weise and 1.3. Kopin, Amer. 3. Physiol. 220, 928 (1971).
15.
R. Kvet~anskj, in: Frontiers in Catecholamine Research, Pergamon Press, Oxford, 1973, p.223.
16,
D. Chuang, C. Zsilla
and E. Costa, Mol. Pharmacol.
on the
11, 784 (1975).
Ther.