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THE MECHANISM OF PRESSOR AND DEPRESSOR RESPONSES TO ELECTRICALLY INDUCED CONVULSION
Jap. J. Pharmacol.2, 1 6 (1952)
THE
MECHANISM TO
OF PRESSOR
ELECTRICALLY KIYOSHI
AND
DEPRESSOR
INDUCED
TANAKA
RESPONSES
CONVULSION
AND NOBORU KAN
Department of Pharmacology,Tottori UniversitySchoolof Medicine, Yonago Received for publication March 3, 1952
Though no objection has been offered to the reports of various authors (1, 2, 3, 4), stating that the blood pressure changes distinctly during and after the elec trically induced convulsion, the detailed mechanism of the change remains to be elucidate. Recently Schoetensack and Hann (5) have given a new interpretation of the mechanism based on their experiment in cats. They found that the blood pres sure simply rose and never fell below the normal level after electroshock in un anesthetized and curarized cats, while it was merely depressed in animals anesthe tized with barbiate. According to them, the pressor response was abolished by yohimbin and therefore it was attributed to the secretion. of epinephrine, and the depressor response was potentiated by eserine and prevented byy atropine, indicating that acetylcholine was liberated. For the last several years we have been engaged in a research on the physio logical changes induced by electroshock in experimental animals and have ascer tained that the responses of blood pressure were not attributable solely to the liberation Qf chemical transmitters such as epinephrine or acetylcholine (o'. The present report presents the results of our experiments and our view on the nature of the pressor and depressor responses to electroshock. Method ; Rabbits were used in every experiment. Electric current was ap plied through needle electrodes placed subcutaneously at the roots of both ears. Stimulation with 50 V. AC 1 sec. was sufficient to induce general tonic and clonic convulsion. Blood pressure was recorded on a smoked drum from the canule inserted in the carotid artery. A. In
normal
through hardly
Typical Changes of Blood Pressure During
the any
The Right
unanesthetized following
influence
1st phase-a after
four
rabbits phases
on the typical transient
the electric
the
change
as shown
and After Convulsion of blood
pressure
in Fig. 1. Urethane
passes
narcosis
has
changes.
depressor
stimulation,
response. a slight
depressor
response
of short
du
FIG. 1.
ration
often
Four
tak~s
tion is shorter
place.
than
intense
sion becomes 50-100
clonic,
pressure
change
The drop' is usually This phase
mighty
At the beginning and
of typical
10 sec.
The 2nd phase-a sudden
phases
of tonic rise,
pressor
the blood
less than
is sometimes
to electroshock.
10 mm Hg and the
totally
dura
lacking.
response.
convulsion
reaching
due
the blood pressure
its maximum
pressure
begins
within
takes
25 sec..
to descend.
a
turn
for
a
When the convul
The height
is usually
mm Hg.
The 3rd phase-a
postconvulsive
When the convulsion down to 10-30
mm Hg below normal.
The 4th phase-a Recovered
from
but long lasting B.
later
Mechanism cessation
mulation,
and
either
vagotomy
(Fig. 2).
pressor
depression,
(2-5
In an experiment dia or.even
depressor
response.
is over, the blood pressure
continues
This depressor
min.) pressor
symptom
lasts for 30-120 sec..
phase.
is shifted
It is 10-20
of the First Phase, "the Transient of heart
phase
till it comes
response.
the blood pressure
with Nuki's
to drop
cardiotambour
beat
occurring
being
abolished
mm Hg above
normal,.
Depressor Response"
, we found immediately by
on to a slow, slight
.remarkable bradycar after the electric sti
atropine
or
after
FIG. 2. Heart action (HA) and blood pressure (BP) changed by electroshock, [A) before and (B) after bilateral vagotomy.
bilateral
PRESSURE The transient the powerful
pressure
heart
The following tance (1) prevented
data
The pressure by curare
FIG. 3.
caused
-two factors'
of blood vessels
ELECTROSHOCK
by central
therefore, vagal
of the Second Phase, "the Mighty
The first mechanism,
experimental
TO
fall of the first phase,
depression
-C. Mechanism
1.
RESPONSES
due
are which
must
to general
will support rise
considered tetanic
of
stimulation. Pressor Response" with
factor,
convulsion.
this phase.
is increased
The
following
resis several
this consideration.
was almost
as shown
must be the result
to be concerned
be the major
3
eliminated
when
the
convulsion
had
been
in Fig. 3.
Pressure change due to electroshock applied after administration of curare; CA) after intravenous injection of 3 mg/kg curare , [B) 5 min. later, under artificial respiration.
We could hardly find such a case as was reported by Schoetensack and Hann , in which only the pressor response without the depressor .phase can occur after the application of curare; we rather noticed that the depressor phase often be came more distinct. This divergence of result may be due to the difference in experimental animals used : the unanesthetized cat and the anesthetized rabbit . (2) The pressor reaction lessened when the convulsion was weakened by general anesthesia with ether, chloroform, alcohol or barbiturate, and the reaction was made marked by a violent convulsion occurring after the administration of morphine or-sodium bicarbonate. (3) In the Nolf's 3-manometer experiment, the fluctuation of the femoral per.ipheral pressure on the denervated and accordingly not convulsive side was lack ing the mighty pressor phase though the later pressor phase , was more obvious, while on the , innervated side it underwent the same change as .the carotid :pres sure (Fig. 4). (4) Bastiani and Piotti (7) expressed their opinion that the compression. of the_ visceral blood vessels in abdominal and thoracal organs due to tetanic convul. sion might, by the cause of the pressor response to electroshock. The compres sion they assumed may of course be regarded as a factor to increase the . resis--_, tance of blood vessels, and the reduction in the pressor effect , observed. in our experiment after removal _of. the majority of the abdominal organs, will support their opinion.
K. TANAKA
FIG. 4.
Experiment pressure pressure.
with
Nolf's
of denervated
2. The second mechanism mulation of the vasomotor autonomic centers, there have cording to the results of these trically stimulated vasomotor
& N. KAN
3-manometer; side;
D:
N : innervated
femoral side;
peripheral C : carotid
of the pressor response consists in the direct sti center. Since Hess's profound investigation of been many studies on the vasomotor center. Ac researches it may seem quite natural that the elec center should induce an active, contraction of
general blood vessels. The facts recognized in our experiment ; namely, that the ear vessels which should not be influenced by muscle contraction were highly contracted during convulsion, and that curare did not completely. abolish the pressor response, may be explicable by the central vasomotor stimulation. D. Mechanism of the Third Phase, " the PostcOf+ulsi ve Depressor Phase" Many factors are conceivable in connection 1. After convulsion the animal falls into a relaxation of all muscles. This may reduce the invite a pressure fall. 2. Stimulation of the vasodilator center is
with this phase. state of narcosis, accompanied by resistance of blood vessels and also possible.
Kurozu's
finding
(8), that when stimulated simultaneously the parasympathetic vasodilator center is irritated later than the sympathetic vasoconstrictor center, corresponds with our experimental result that the depressor phase follows the mighty pressor phase. 3. Heart depression may be another factor. Hejtmaneik (9) and Altschule (10) observed a remarkable reduction in heart rate in the human electrocardio gram during electroshock, and Wada (1) supposed the pressure fall to be due to cardiac depression. In our experiment on the rabbit, however, bradycardia was insignificant in this depressor phase, while it was remarkable in the first and pressor phases, and furthermore it was abolished by atropine though the pressure fall was not
PRESSURE
RESPONSES
TO
ELECTROSHOCK
influenced
by the drug . We cannot, therefore, accept sion is the chief factor in this phase . 4. Schoetensack and Hann assumed the liberation main
factor
in the pressure
not prevented ed after
by atropine
atropine
of cholinesterase
beneficial
to the
pose that
acetylcholine
1.
during
after
may
may
Bilateral
the view that
heart
of acetylcholine
however
that
depres to be the
this depression
was
bradycardia completely disappear (Fig . 2). On the other hand, the reported by Neustadt (11), may be
electroshock
accumulation
. We should, therefore, play some, if not, the chief role in the pressure
sup fall.
of the Fourth Phase, " the Later Pressor Response "
be assumable
in this phase . or ergotamine administration
adrenalectomy
phase
in this phase,
in the rabbit , while or vagotomy
idea of acetylcholine
E. Mechanism Two factors
We confirmed
administration
reduction
this pressor
fall.
5
or the depression
but these
of intestine
managements
did not
motility affect
, which the first
abolished usually pressor
either
appeared response
convulsion
(Fig. 5) . Epinephrine liberation is, therefore, most responsible for the appearance of this phase . Schoetensack's opinion, that the pressor res ponse is due to epinephrine, is acceptable only so far as the fourth phase is con cerned in our case .
FIG. 5.
2. our
We noticed
results
on animals relieves bility
Blood pressure (BP) and intestine motility (IM) changed by electroshock : (A) before and (B) after bilateral adrenalec tom y.
reported
of turning
this
before,
anesthetized
animals
irritation
that
phase
is distinct
indicating urethane
that
of the awakening
or
electroshock
from
alcohol
has
animals , and from an awaking effect
(12), and that electroshock from severe barbiturate poisoning (13), we can suggest the possi the vasomotor center from the state of depression to that of
as a result
with
in anesthetized
narcosis ,
6
K.
TANAKA
& N.
KAN
CONCLUSION During sure
rises
sidered 1.
and and
falls through
The first The
transient
second
mighty
increases
also invite
vessel
3.
vessel
convulsion
phases.
The mechanism
dilator
center,
liberation The
resistance.
in rabbits,
the blood
of each
heart
fourth
the adrenal
is mainly Direct
and consequently
depression later
is due to the heart
state
after
the result
central
phase
pres is con
chiefly
convulsion.
due to central
depression
caused
of general
convul
vasomotor
pressure
phase may be induced
in the narcotic
are considered
phase
center . pressor phase
contraction
The third depressor
of blood vessels
4.
four
induced
depressor
of the vagal
sion which
from
electrically
as follows :
by stimulation 2.
after
stimulation
rise. by decreased Stimulation
vagal stimulation
resistance of the
vaso
and acetylcholine
to be side factors. pr essor
phase
is ascribable
to epinephrine
secretion
glands. REFERENCES
1) WADA, J.: Folia Psychol. Neuyol. Japon. 3, 302 (1949) 2) KANAZAWA,T.: Niigata Med. J. 63, 228 (1949) 8) ITO, S. et al.: J. Tokyo Med. College 8, 48 (1950) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13)
can
PIETTE, V.: Ann. Soc. Roy. Sci. Med. 3, 5 (1950) SCHOETENSACK, W. AND HANN, J.: Arch. exper. Path. u. Pharmakol. 213, 102 (1951) KAN, N.: Folia pharmacol. japon. 48, 42 (1952) BASTIANI,G. AND PIOTTI, 0.: Arch. di Sci. Biol. 33, 489 (1949) KUROZU,T. et al.: No-Kenkyu 3, 57 (1949) HEJTMANEIK,M. R. et al.: Amer . Heart J. 37, 790 (1949) ALTSCHULE,M. D. et al.: Arch. Neurol. Psychiat. 58, 653 (1947) NEUSTADT,R. et al.: Cit. f. Arch. Neurol. Psychiat. 63, 336 (1950) TANAKA, K. AND KAN, N .: Seitai no Kagaku 2, 237 (1951) TANAKA, K. AND KAN, N.: J . lonago Med. Ass. 3, 22 (1951)
THE
MECHANISM TO
OF PRESSOR
ELECTRICALLY KIYOSHI
AND
DEPRESSOR
INDUCED
TANAKA
RESPONSES
CONVULSION
AND NOBORU KAN
Department of Pharmacology,Tottori UniversitySchoolof Medicine, Yonago Received for publication March 3, 1952
Though no objection has been offered to the reports of various authors (1, 2, 3, 4), stating that the blood pressure changes distinctly during and after the elec trically induced convulsion, the detailed mechanism of the change remains to be elucidate. Recently Schoetensack and Hann (5) have given a new interpretation of the mechanism based on their experiment in cats. They found that the blood pres sure simply rose and never fell below the normal level after electroshock in un anesthetized and curarized cats, while it was merely depressed in animals anesthe tized with barbiate. According to them, the pressor response was abolished by yohimbin and therefore it was attributed to the secretion. of epinephrine, and the depressor response was potentiated by eserine and prevented byy atropine, indicating that acetylcholine was liberated. For the last several years we have been engaged in a research on the physio logical changes induced by electroshock in experimental animals and have ascer tained that the responses of blood pressure were not attributable solely to the liberation Qf chemical transmitters such as epinephrine or acetylcholine (o'. The present report presents the results of our experiments and our view on the nature of the pressor and depressor responses to electroshock. Method ; Rabbits were used in every experiment. Electric current was ap plied through needle electrodes placed subcutaneously at the roots of both ears. Stimulation with 50 V. AC 1 sec. was sufficient to induce general tonic and clonic convulsion. Blood pressure was recorded on a smoked drum from the canule inserted in the carotid artery. A. In
normal
through hardly
Typical Changes of Blood Pressure During
the any
The Right
unanesthetized following
influence
1st phase-a after
four
rabbits phases
on the typical transient
the electric
the
change
as shown
and After Convulsion of blood
pressure
in Fig. 1. Urethane
passes
narcosis
has
changes.
depressor
stimulation,
response. a slight
depressor
response
of short
du
FIG. 1.
ration
often
Four
tak~s
tion is shorter
place.
than
intense
sion becomes 50-100
clonic,
pressure
change
The drop' is usually This phase
mighty
At the beginning and
of typical
10 sec.
The 2nd phase-a sudden
phases
of tonic rise,
pressor
the blood
less than
is sometimes
to electroshock.
10 mm Hg and the
totally
dura
lacking.
response.
convulsion
reaching
due
the blood pressure
its maximum
pressure
begins
within
takes
25 sec..
to descend.
a
turn
for
a
When the convul
The height
is usually
mm Hg.
The 3rd phase-a
postconvulsive
When the convulsion down to 10-30
mm Hg below normal.
The 4th phase-a Recovered
from
but long lasting B.
later
Mechanism cessation
mulation,
and
either
vagotomy
(Fig. 2).
pressor
depression,
(2-5
In an experiment dia or.even
depressor
response.
is over, the blood pressure
continues
This depressor
min.) pressor
symptom
lasts for 30-120 sec..
phase.
is shifted
It is 10-20
of the First Phase, "the Transient of heart
phase
till it comes
response.
the blood pressure
with Nuki's
to drop
cardiotambour
beat
occurring
being
abolished
mm Hg above
normal,.
Depressor Response"
, we found immediately by
on to a slow, slight
.remarkable bradycar after the electric sti
atropine
or
after
FIG. 2. Heart action (HA) and blood pressure (BP) changed by electroshock, [A) before and (B) after bilateral vagotomy.
bilateral
PRESSURE The transient the powerful
pressure
heart
The following tance (1) prevented
data
The pressure by curare
FIG. 3.
caused
-two factors'
of blood vessels
ELECTROSHOCK
by central
therefore, vagal
of the Second Phase, "the Mighty
The first mechanism,
experimental
TO
fall of the first phase,
depression
-C. Mechanism
1.
RESPONSES
due
are which
must
to general
will support rise
considered tetanic
of
stimulation. Pressor Response" with
factor,
convulsion.
this phase.
is increased
The
following
resis several
this consideration.
was almost
as shown
must be the result
to be concerned
be the major
3
eliminated
when
the
convulsion
had
been
in Fig. 3.
Pressure change due to electroshock applied after administration of curare; CA) after intravenous injection of 3 mg/kg curare , [B) 5 min. later, under artificial respiration.
We could hardly find such a case as was reported by Schoetensack and Hann , in which only the pressor response without the depressor .phase can occur after the application of curare; we rather noticed that the depressor phase often be came more distinct. This divergence of result may be due to the difference in experimental animals used : the unanesthetized cat and the anesthetized rabbit . (2) The pressor reaction lessened when the convulsion was weakened by general anesthesia with ether, chloroform, alcohol or barbiturate, and the reaction was made marked by a violent convulsion occurring after the administration of morphine or-sodium bicarbonate. (3) In the Nolf's 3-manometer experiment, the fluctuation of the femoral per.ipheral pressure on the denervated and accordingly not convulsive side was lack ing the mighty pressor phase though the later pressor phase , was more obvious, while on the , innervated side it underwent the same change as .the carotid :pres sure (Fig. 4). (4) Bastiani and Piotti (7) expressed their opinion that the compression. of the_ visceral blood vessels in abdominal and thoracal organs due to tetanic convul. sion might, by the cause of the pressor response to electroshock. The compres sion they assumed may of course be regarded as a factor to increase the . resis--_, tance of blood vessels, and the reduction in the pressor effect , observed. in our experiment after removal _of. the majority of the abdominal organs, will support their opinion.
K. TANAKA
FIG. 4.
Experiment pressure pressure.
with
Nolf's
of denervated
2. The second mechanism mulation of the vasomotor autonomic centers, there have cording to the results of these trically stimulated vasomotor
& N. KAN
3-manometer; side;
D:
N : innervated
femoral side;
peripheral C : carotid
of the pressor response consists in the direct sti center. Since Hess's profound investigation of been many studies on the vasomotor center. Ac researches it may seem quite natural that the elec center should induce an active, contraction of
general blood vessels. The facts recognized in our experiment ; namely, that the ear vessels which should not be influenced by muscle contraction were highly contracted during convulsion, and that curare did not completely. abolish the pressor response, may be explicable by the central vasomotor stimulation. D. Mechanism of the Third Phase, " the PostcOf+ulsi ve Depressor Phase" Many factors are conceivable in connection 1. After convulsion the animal falls into a relaxation of all muscles. This may reduce the invite a pressure fall. 2. Stimulation of the vasodilator center is
with this phase. state of narcosis, accompanied by resistance of blood vessels and also possible.
Kurozu's
finding
(8), that when stimulated simultaneously the parasympathetic vasodilator center is irritated later than the sympathetic vasoconstrictor center, corresponds with our experimental result that the depressor phase follows the mighty pressor phase. 3. Heart depression may be another factor. Hejtmaneik (9) and Altschule (10) observed a remarkable reduction in heart rate in the human electrocardio gram during electroshock, and Wada (1) supposed the pressure fall to be due to cardiac depression. In our experiment on the rabbit, however, bradycardia was insignificant in this depressor phase, while it was remarkable in the first and pressor phases, and furthermore it was abolished by atropine though the pressure fall was not
PRESSURE
RESPONSES
TO
ELECTROSHOCK
influenced
by the drug . We cannot, therefore, accept sion is the chief factor in this phase . 4. Schoetensack and Hann assumed the liberation main
factor
in the pressure
not prevented ed after
by atropine
atropine
of cholinesterase
beneficial
to the
pose that
acetylcholine
1.
during
after
may
may
Bilateral
the view that
heart
of acetylcholine
however
that
depres to be the
this depression
was
bradycardia completely disappear (Fig . 2). On the other hand, the reported by Neustadt (11), may be
electroshock
accumulation
. We should, therefore, play some, if not, the chief role in the pressure
sup fall.
of the Fourth Phase, " the Later Pressor Response "
be assumable
in this phase . or ergotamine administration
adrenalectomy
phase
in this phase,
in the rabbit , while or vagotomy
idea of acetylcholine
E. Mechanism Two factors
We confirmed
administration
reduction
this pressor
fall.
5
or the depression
but these
of intestine
managements
did not
motility affect
, which the first
abolished usually pressor
either
appeared response
convulsion
(Fig. 5) . Epinephrine liberation is, therefore, most responsible for the appearance of this phase . Schoetensack's opinion, that the pressor res ponse is due to epinephrine, is acceptable only so far as the fourth phase is con cerned in our case .
FIG. 5.
2. our
We noticed
results
on animals relieves bility
Blood pressure (BP) and intestine motility (IM) changed by electroshock : (A) before and (B) after bilateral adrenalec tom y.
reported
of turning
this
before,
anesthetized
animals
irritation
that
phase
is distinct
indicating urethane
that
of the awakening
or
electroshock
from
alcohol
has
animals , and from an awaking effect
(12), and that electroshock from severe barbiturate poisoning (13), we can suggest the possi the vasomotor center from the state of depression to that of
as a result
with
in anesthetized
narcosis ,
6
K.
TANAKA
& N.
KAN
CONCLUSION During sure
rises
sidered 1.
and and
falls through
The first The
transient
second
mighty
increases
also invite
vessel
3.
vessel
convulsion
phases.
The mechanism
dilator
center,
liberation The
resistance.
in rabbits,
the blood
of each
heart
fourth
the adrenal
is mainly Direct
and consequently
depression later
is due to the heart
state
after
the result
central
phase
pres is con
chiefly
convulsion.
due to central
depression
caused
of general
convul
vasomotor
pressure
phase may be induced
in the narcotic
are considered
phase
center . pressor phase
contraction
The third depressor
of blood vessels
4.
four
induced
depressor
of the vagal
sion which
from
electrically
as follows :
by stimulation 2.
after
stimulation
rise. by decreased Stimulation
vagal stimulation
resistance of the
vaso
and acetylcholine
to be side factors. pr essor
phase
is ascribable
to epinephrine
secretion
glands. REFERENCES
1) WADA, J.: Folia Psychol. Neuyol. Japon. 3, 302 (1949) 2) KANAZAWA,T.: Niigata Med. J. 63, 228 (1949) 8) ITO, S. et al.: J. Tokyo Med. College 8, 48 (1950) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13)
can
PIETTE, V.: Ann. Soc. Roy. Sci. Med. 3, 5 (1950) SCHOETENSACK, W. AND HANN, J.: Arch. exper. Path. u. Pharmakol. 213, 102 (1951) KAN, N.: Folia pharmacol. japon. 48, 42 (1952) BASTIANI,G. AND PIOTTI, 0.: Arch. di Sci. Biol. 33, 489 (1949) KUROZU,T. et al.: No-Kenkyu 3, 57 (1949) HEJTMANEIK,M. R. et al.: Amer . Heart J. 37, 790 (1949) ALTSCHULE,M. D. et al.: Arch. Neurol. Psychiat. 58, 653 (1947) NEUSTADT,R. et al.: Cit. f. Arch. Neurol. Psychiat. 63, 336 (1950) TANAKA, K. AND KAN, N .: Seitai no Kagaku 2, 237 (1951) TANAKA, K. AND KAN, N.: J . lonago Med. Ass. 3, 22 (1951)