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Johannes-Müller-Institut für Physiologie, Humboldt-Universität zu Berlin (Charité), 10117 Berlin, Germany; and Department of Exercise Science, University of Iowa, Iowa City, Iowa 52242
THE IMPORTANCE of the baroreceptor
reflex is to stabilize perfusion pressure in the face of disturbances
of circulatory homeostasis. This is achieved by a number of neuronal
(8, 29, 37, 48) and humoral (37, 45, 46)
regulatory adjustments. These adjustments are initiated by a change in
the pressure load at specialized pressure sensors located at the aortic
arch and the carotid sinuses. Especially with regard to experiments
involving sinoaortic denervation (6, 13, 14, 20, 31), it
is important to note that these two pressure-sensitive sites are not
equivalent with respect to defending arterial blood pressure during
hypotensive challenges, such as hypovolemia. In conscious dogs, blood
pressure started to decline at a lower volume of hemorrhage in carotid
baroreceptor-denervated animals compared with animals with disrupted
aortic baroreceptors (47). Thus, in dogs, the carotid
baroreceptors are required to achieve a normal blood pressure response
to hemorrhage. In addition, they are able to compensate for the loss of
aortic baroreceptor function.
At resting blood pressure levels, the majority of baroreceptor
afferents are providing a tonic, excitatory input to neurons in the
nucleus of the solitary tract (NTS), where these peripheral afferents
make their initial synapses (49). However, the blood pressor increase in response to bilateral common carotid artery occlusion is enhanced in commissural NTS-lesioned rats
(41). Thus the termination of baroreceptor afferents is
more widespread and other regions than the commissural NTS are also
involved. The NTS constitutes the brain stem site for afferent
baroreceptor inputs, whereas the rostral ventrolateral medulla (RVLM)
is the output site for baroreceptor reflex modulation of efferent
sympathetic nerve activity. Beside the RVLM, the activity of other
nuclei is also modulated by the baroreceptor reflex. The primary
stimulus for vasopressin release from the supraoptic nucleus is
osmolality (5, 38). However, the baroreceptor reflex
exerts an additional regulatory input to supraoptic
vasopressin-releasing neurons (19, 20, 45, 46).
Two parameters are often determined to estimate baroreceptor reflex
function. First is the operating point of the reflex, i.e., arterial
pressure, at which the reflex responds most effectively to changes in
arterial pressure. Second is the sensitivity of the reflex, i.e., the
magnitude of the reflex response per unit of arterial blood pressure
deviation from the operating point. In addition to these two
traditional parameters, a baroreflex effectiveness index has recently
been proposed that may provide information on how active the
baroreceptor reflex is involved in blood pressure and heart rate
regulation (11, 44).
The RVLM receives inputs from a variety of central nervous system areas
directly or indirectly linked to baroreceptor reflex function, such as
the NTS (10, 30, 34, 43), the medullary lateral tegmental
field (3), or the ventrolateral periaqueductal gray
(2, 17). The natural discharge pattern of RVLM spinal neurons is synchronized with the cardiac rhythm, and baroreceptor activation decreases the activity of these neurons. Furthermore, suppression of RVLM neurons by local injection of an imidazoline receptor agonist decreased the sensitivity of the baroreceptor-renal sympathetic nerve activity reflex in conscious chronically instrumented rabbits (35). Conversely, excitation of the RVLM via
microinjections of glutamate increased the sensitivity of the
baroreceptor-renal sympathetic nerve activity and the
baroreceptor-heart rate reflex (35). Thus the sensitivity
of the baroreceptor reflex appears to be directly related to the
neuronal activity within the pressure region of the RVLM.
Recently, the role of 5-hydroxytryptamine 1A [5-HT(1A)] receptors
within the RVLM in mediating sympathoinhibition and baroreceptor reflex
function was studied in anesthetized rats (2, 9, 36).
Microinjection into the RVLM of a selective 5-HT(1A) receptor agonist
decreased arterial blood pressure and peripheral sympathetic nerve
activity (36), whereas microinjection of a specific
5-HT(1A) receptor antagonist attenuated or even reversed the
sympathoinhibitory and hypotensive response to activation of the
ventrolateral periaqueductal gray matter of the midbrain
(2). Furthermore, the hypotensive and sympathoinhibitory
effect of severe hemorrhage, a baroreceptor-independent response, was
attenuated by microinjection of a specific 5-HT(1A) antagonist into the
RVLM (9). However, baroreceptor reflex inhibition of renal
sympathetic nerve activity in response to a hypertensive challenge
evoked by intravenous administration of phenylephrine was not altered
by the 5-HT(1A) receptor antagonist (2). Furthermore, the
depressor and splanchnic sympathoinhibitory response to supramaximal
aortic nerve stimulation was also not altered by the specific 5-HT(1A)
receptor agonist (36). Thus 5-HT(1A) receptors do not
appear to be involved in baroreceptor reflex modulation within the
RVLM, but they are important for the regulation of basal sympathetic
outflow to the periphery.
The operating point and the sensitivity of the baroreceptor reflex are
altered in physiological and pathophysiological situations, such as
development (1, 21), aging (25), pregnancy
(23, 24), different sleep states (40), and
hypertension (15). Baroreflex function is also altered
during thermoregulation. In conscious unrestrained rats, hyperthermia
caused a shift in the operating point of the baroreceptor-heart rate
and baroreceptor-sympathetic nerve activity reflex to higher blood
pressure levels (33). This resetting of the reflex
guarantees that the reflex continues to operate at a high gain despite
the pressure rise that accompanies hyperthermia. Reflex-mediated
changes in sympathetic tone can have a dramatic impact on
thermoregulation, as demonstrated in patients undergoing lower
abdominal surgery (39). Baroreceptor loading by a leg-up
position caused cutaneous vasodilation and subsequent hypothermia. This
effect is attenuated by positive end-expiratory pressure ventilation
(39) thought to operate via baroreceptor unloading.
Exercise is also accompanied by a modulation of baroreceptor reflex
function, as indicated by microneurography of muscle sympathetic nerve
fibers of the tibial nerve during static handgrip exercise
(29). In this study, the sensitivity of the
baroreceptor-muscle sympathetic nerve activity reflex was increased by
more than 300%. Thus an increase in arterial blood pressure during
exercise is associated with a three times greater reduction in
sympathetic nerve activity compared with resting conditions. This may
be seen as a protective mechanism that buffers the degree of
sympathoexcitation evoked by the exercise pressor reflex
(22). In this regard, a differential baroreflex regulation of vascular conductance in working (iliac) and nonworking (mesenteric) vascular beds has been reported in rats during dynamic treadmill exercise (32). Under these conditions, an increase in
arterial blood pressure caused a greater increase in iliac than in
mesenteric vascular conductance. The differential regulation of
baroreceptor reflex-mediated control of vascular conductance helps to
preserve a proper blood supply of the working skeletal muscle.
Hypovolemia frequently leads to orthostatic dysfunction, which is a
common problem after prolonged bed rest or in astronauts after return
from spaceflights (4, 7, 12, 26-28). It has been
demonstrated that hypovolemia is associated with a reduced baroreceptor-heart rate reflex and an augmented baroreceptor-muscle sympathetic nerve activity reflex (26). The symptoms of
hypovolemia-related orthostatic dysfunction, such as hypotension
(42) or a decrease in central venous pressure
(18), can be reduced by the application of lower body
positive pressure. As assessed by microneurography of the tibial nerve,
this maneuver also attenuates the sympathoexcitation associated with
orthostatic challenges (16). Thus application of lower
body positive pressure normalizes the baroreceptor-muscle sympathetic
nerve activity reflex that is often enhanced in patients with
orthostatic dysfunction (27).
Knowledge about the neuronal pathways and neurotransmitter systems
involved in the adjustments of baroreceptor reflex function to
physiological and pathophysiological conditions has increased substantially in the last few years but is still far from being completely understood. Further regulatory, integrative, and comparative studies are needed to address these issues.
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Address for reprint requests and other correspondence: H. M. Stauss, Dept. of Exercise Science, Univ. of Iowa, Field House, Iowa City, IA 52242.
10.1152/ajpregu.00219.2002
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