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Clinical Science and Molecular Medicine (1976) 51, 353s-355s.
Cardiac reflexes conducted by vagal afferents in
normotensive and renal hypertensive dogs
P. KEZDI
Cox Heart Institute, Dayton, Ohio, U.S.A.
baroreflexes in the tonic regulation of the blood
pressure and their possible participation in the
altered blood pressure regulation of hypertension.
summary
1. The renal sympathetic reflex responses to
transient balloon occlusion of the descending aorta
(systemic baroreceptor activation) and the ascending
aorta (cardiac stretch-receptor activation) have
been studied together with blood pressure increases
after successive cutting of carotid sinus, aortic
and vagus nerves in acute experiments in the dog.
2. Results from these experiments provide evidence
for cardiac vagal afferent participation in the tonic
regulation of systemic blood pressure.
3. In other experiments the reflex pressureresponse curve of the isolated gracilis muscle at
constant flow to transient ascending aorta occlusion
was measured. This curve was moved to the right in
renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left
ventricular pressure in the former.
3. These findings indicate resetting of ventricular
receptors in hypertensive animals.
Methods
Key words : blood pressure, hypertension, vagal
afferents, ventricular receptors.
Introduction
Reflexes originating in the heart have been traced
to the atria, the ventricles and the coronary arteries
(Shepherd, 1973; Linden, 1975). Afferent pathways
are mostly in the vagus nerves and impulses are
conducted by myelinated and non-myelinated
fibres. The clinical role of the ventricular receptors
is little known.
We have been interested in the role of cardiac
Correspondence: Dr Paul Kezdi, Cox Heart Institute,
3525 Southern Boulevard, Dayton, Ohio, U.S.A.
Experiments were performed in mongrel dogs of
both sexes. Three groups were studied. Group 1 was
composed of eight normotensive dogs in which reflex
changes of sympathetic nerve activity were recorded
in response to temporary occlusion of the descending
and ascending aorta before and after successive
cutting of the systemic baroreceptors. The renal
nerve was isolated by retroperitoneal approach to
isolate the kidney. In group 2 (eight normotensive
dogs) and group 3 (six renal hypertensive dogs)
reflex changes in perfusion pressure of the isolated
constant-flow gracilis muscle were recorded in
response to graded temporary occlusion of the
ascending aorta. Hypertension was produced by
cellophan wrapping of one kidney and contralateral
nephrectomy.
Temporary occlusion of the aorta was produced by
a balloon catheter, which was introduced through
a left carotid artery. The tip of this catheter was
advanced into the left ventricle to measure left
ventricular pressure while the balloon was in the
ascending portion of the aorta, about 1 cm above the
aortic valve. A graded increase of left ventricular
pressure could be produced by inflating the balloon
to different degrees. Occlusion of the descending
aorta in group 1 dogs was carried out by a similar
catheter introduced through the femoral artery to
the mid-portion of the thoracic aorta.
The gracilis muscle artery was perfused by a
roller pump with arterial blood from the opposite
femoral artery. A flow probe was placed on the
gracilis muscle artery and the flow was adjusted
353s
354s
P. Kezdi
so that the perfusion pressure approximated to
base-line systemic pressure. Pressure was measured
by Statham P53D strain gauges through a catheter
from a side branch of the artery.
At the completion of the gracilis perfusion
pressure recordings, the left vagus was isolated
and fibres were separated to record afferent nerve
activity from the left ventricle in response to graded
occlusion of the ascending aorta (group 2 and group
3 only).
For nerve activity multifibre and single-fibre
recordings were made with platinum-iridium bipolar
electrodes, Tektronic 122 low level preamplifier,
Astrodata amplifiers and Honeywell 1507 Visicorder.
At the termination of the experiment the chest was
opened and the location of the receptors from which
recordings were made was identified after stopping
the heart by an overdose of intravenous sodium
pentobarbitone (Nembutal). Localized pressure
was applied to the wall of the left ventricle at different points with a cotton-covered haernostat.
The dogs were anaesthetized with chloraloseurethane, respired by a Harvard animal respirator
and paralysed by succinylcholine to prevent muscle
artifacts. The carotid sinus and aortic nerves were
isolated in the neck in each experiment and identified
electroneurographically for later selective cutting.
The aortic nerve was isolated at the junction of the
vagus with the superior laryngeal nerve. Care was
taken not to damage the rest of the vagus nerve.
Results
arily occluded, however, raising the left ventricular
pressure even higher (with systemic pressure dropping to 30 mmHg) there was marked sympathetic
inhibition irrespective of whether or not the systemic
baroreceptor nerves were intact or cut. Cutting
the vagus nerves further increased base-line sympathetic activity and eliminated the reflex inhibition
by occlusion of the ascending aorta.
Reflex response of gracilis muscle perfusion pressure
The mean arterial pressure in norrnotensive dogs
was 90 mmHg and in hypertensive dogs was 135
mmHg.
-.OI
-50
Mean LV pressure (mmHg)
Reflex inhibition of renal sympathetic nerve activity
FIG.1. Perfusion pressure response for the gracilis muscle
artery to gradual increase of left ventricular (LV) mean
In group 1 dogs renal sympathetic nerve,activity
was first recorded with all systemic baroreceptors
intact. Temporary occlusion of the descending
aorta was then carried out to raise the pressure
in the entire aortic arch. This resulted in reflex
inhibition of sympathetic activity. After release
of the occlusion and re-establishing base-line sympathetic activity, blood pressure and heart rate,
cutting of both carotid sinus nerves increased baseline sympathetic activity and decreased the reflex
inhibition of sympathetic activity by temporary
occlusion of the descending aorta. Subsequently
when the aortic nerves were cut, renal sympathetic
activity further increased and reflex inhibition to
temporary occlusion of the descending aorta was
not present. When the ascending aorta was tempor-
pressure in normotensive ( 0 ) and hypertensive (M) dogs.
In normotensive (group 2) dogs the gracilis
muscle perfusion pressure showed the first decrease
to temporary graded balloon occlusion of the
ascending aorta when the mean left ventricular
pressure was increased from 47 to 73 mmHg
average (threshold response). With a more marked
increase of the left ventricular pressure further
decrease of the gracilis muscle perfusion pressure
occurred. Maximum pressure decrease was reached
when left ventricular mean pressure was raised to
150 mmHg (see Fig. 1).
Graded increase of left ventricular pressure in
hypertensive dogs showed the first response of the
gracilis perfusion pressure at 102 mmHg mean left
Cardiac reflexes in normo- and hyper-tension
ventricular pressure, compared with 73 mmHg
in the normotensive dogs. A maximum response was
reached at 174 mmHg. The gracilis muscle perfusion
pressure-response curve was shifted to the right in
response to left ventricular pressure increase in the
hypertensive dogs when compared with the normotensive dogs (see Fig. 1).
Vagal afferent nerve activity
Vagal afferent nerve activity from ventricular
receptors showed sparse pulse synchronous discharges at base-line pressures, both in normotensive
and hypertensive dogs. When gradual balloon
occlusion of the ascending aorta was carried out,
pressure in the left ventricle increased and pressure
in the aorta beyond the occlusion rapidly decreased.
Afferent vagal nerve activity increased, first by pulse
synchronous discharge and then by continuous
activity as the pressure was further increased in the
left ventricle. In hypertensive animals, the threshold
pressure at which new receptors were recruited was
at a higher left ventricular pressure. Atrial nerve
activity was also increased slightly during balloon
occlusion but never became continuous.
Discussion
The experiments with group 1 dogs confirm that
cardiopulmonary vagal afferent fibres play a role
in the tonic regulation ofthe circulation as indicated
by the additional increase of post-ganglionic
sympathetic nerve discharge after cutting of the
vagus nerves, after the carotid sinus and aortic
nerves have previously been cut. Cardiopulmonary
vagal afferent pathways exert a powerful reflex
inhibition of sympathetic discharge, decrease of
355s
heart rate and blood pressure. Receptors of this
reflex are located predominantly in the left ventricle.
Left atrial distension (volume increase) was shown
by Mason & Ledsome (1974) to affect predominantly
renal vascular resistance but not resistance in the
isolated perfused hind limb.
The threshold of the ventricular receptors is
significantly higher than the threshold of systemic
baroreceptors, the aortic nerve receptors having a
higher threshold than the carotid sinus receptors.
VentricJar receptors are activated probably only
when ventricular pressure is raised to a considerably
high value. However, pressures which stimulate
ventricular receptor activity can be present in
hypertension.
It appears that the threshold and the range of the
reflex activity of the ventricular receptors shift to
the right in chronic renal hypertensive dogs. This
would be analogous to the changes which occur in the
threshold of systemic baroreceptors. This is probably
due to the decreased compliance of the left ventricle
in hypertension and is part of the general autonomic
nervous system resetting which takes place.
Acknowledgment
Supported by grant HL 15004 of the National
Institute of Health.
References
LINDEN,R.J. (1975) Reflexes from the heart. Progress in
Cardiovascular Disease, 18, 201-221.
MASON,J.M. & LEDSOME,
J.R. (1974) Effects of obstruction
of the mitral orifice or distension of the pulmonary veinatrial junctions on renal and hind-limb vascular resistance
in the dog. Circulation Research, 35, 24-32.
SHEPHERD,
J.T. (1973) lntrathoracic baroreflexes. Mayo Clinic
Proceedings, 48,42643 7.