VASOMOTION: MECHANISMS AND

PHYSIOLOGICAL IMPORTANCE

asomotion, rhythmic oscillations in vascular tone caused by local changes in smooth

V muscle constriction and dilation, has been observed since the invention of the microscope,

but its physiological role and its underlying mechanism remain elusive. Present in many tissues,

vasomotion might serve as a protective mechanism under conditions of ischemia. Its generation

seems dependent on synchronization of a multitude of individual cellular oscillators. The

concept of calcium release and uptake by the smooth muscle calcium stores, synchronized by

sarcolemmal ion channels, and sometimes influenced by endothelial factors, may provide further

understanding of this little-understood phenomenon.

Holger Nilsson and Christian Aalkjær

The Water and Salt Center and Department of Physiology
University of Aarhus, Universitetsparken, Bldg. 160
DK-8000 Aarhus C, Denmark

March 2003
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 Review

INTRODUCTION vasomotion. This review briefly summarizes the hypothesized

Vasomotion is an oscillation of vascular tone that is generated from
within the vascular wall and is not a consequence of heartbeat,
respiration, or neuronal input. Vasomotion is a phenomenon
observed by many scientists studying vascular physiology,
occurring both in vivo and in vitro (Figure 1) in many vascular
networks if the correct conditions are present. The first detailed
report of vasomotion—in the bat wing—was made more than 150
years ago (1).
In spite of this relatively long history, two important questions
remain incompletely understood: What is the cellular mechanism
responsible for vasomotion? What is the physiological consequence
of vasomotion?
In many experimental contexts vasomotion is problematic; for
example, it is difficult to define specific amounts of tone in an
oscillating vessel and therefore to determine concentration-response
curves unambiguously. Furthermore, vasomotion is frequently
unpredictable and difficult to reproduce; occasionally, experimental
animals cease to exhibit vasomotion for varying periods of time,
and in vitro experiments fail because vasomotion cannot be
replicated. Nevertheless, during the last twenty years, much
progress has been made with respect to the questions of cell-
specific mechanisms and physiological consequences of
mechanisms of vasomotion and discusses some of the physiological
and pathophysiological roles suggested for vasomotion.
OCCURRENCE OF VASOMOTION
Vasomotion has been described both in the intact animal and in
isolated arteries. A summary of the literature on intact animals was
made by Funk and Itaglietta (2) beginning with the observations
made by Jones in 1852 of rhythmic changes in the bat wing (1)
through to the early 1980s. Apart from direct demonstrations of
diameter changes in vessels, the presence of vasomotion has also
been demonstrated by measuring blood-cell velocity (3), capillary
pressure (flow motion) variations (4), or laser-Doppler flow signals
(Box 1) (5). The presence of localized oscillations in blood flow in
human cutaneous circulation has been taken as evidence of the
local, non-nervous origin of the oscillations. In hamsters,
vasomotion has been carefully studied in skin-fold preparations
from both awake and anesthetized animals (6). Vasomotion was
observed in the awake animal but disappeared readily upon
anesthesia with pentobarbital and chloralose–urethane (6). Similarly,
in the cerebral circulation of rabbits, vasomotion is observed under
wakeful conditions and is depressed by anesthesia (7).
In skeletal muscle, vasomotion can be induced after bleeding

Figure 1. Conceptual model for the generation of vasomotion in rat mesenteric small arteries. The basic oscillator is
the sarcoplasmic reticulum (SR), which intermittently releases calcium leading to regenerative waves of calcium traversing the cell (A). In the
presence of cyclic GMP (cGMP), this calcium also is able to activate a chloride channel in the plasma membrane (B). If this current is
activated in a sufficient number of cells at the same time, cells will depolarize (C). Also cells that are not contracting at that moment will
depolarize, because all cells are electrically coupled (D). Depolarization will cause calcium influx through L-type calcium channels (E), which
not only triggers contraction but also calcium release in quiescent cells (F), thus resetting their intracellular oscillators. In this way, the
likelihood for a sufficient number of cells becoming active together in the next cycle is very high, and the cells in effect become phase-locked.
cGMP promotes vasomotion by its permissive action on the ion channel, most likely via protein kinase G–mediated phosphorylation of the
channel, but inhibits vasomotion by actions on the SR by influencing intracellular calcium availability, uptake, and/or release. Differences in
this balance may explain the variable influence of endothelium in vasomotion. Ca2+(V), voltage-gated (L-type) calcium channel; Um,
membrane potential.

80
 Smooth muscle oscillations

Box 1. Methods used in the study of vasomotion.

1. Vital microscopy. Direct observation of the movements of blood vessels has been the traditional method to study vasomotion. While
mostly done in anesthetized animals, implanting a skin window (6) has allowed investigators to inspect blood vessels in underlying
tissue in the awake animal.
2. Pressure measurements. Measuring the pressure in the capillaries after direct cannulation gives a measure of the ratio of pre- to post-
capillary resistance, provided the arteriovenous pressure difference is constant throughout the measurement. The most likely cause of
fluctuations in this ratio is changes in the degree of constriction of precapillary resistance vessels.
3. Blood-cell velocity measurements. The time it takes a cell to pass a certain distance along a capillary is proportional to the volume
flow through the capillary as long as capillary diameter stays constant (a reasonable assumption under most conditions). With the
same provisos as for pressure measurements, variations in flow reflect upstream constrictions, since flow is determined by the
pressure gradient along the capillary.
4. Laser-Doppler flow measurement. Light from a strong, monochromatic light source undergoes a frequency shift (Doppler shift) when
it is backscattered from moving objects; analysis of this shift in backscattered light from living tissue gives a relative measure of blood
cell movement, thus average blood flow in a volume of tissue. This volume is typically hard to define; in other respects the technique
is similar in principle to the blood-cell velocity measurement.
5. Isolated vessels. Studies of excised artery specimens with various kinds of organ-bath techniques have the advantage of examining
strictly local phenomena under well-controlled conditions. For technical reasons these studies are limited to relatively large arteries,
not those that typically are responsible for capillary flow motion in vivo. Still, they may provide some insight into the cellular
mechanisms that can generate oscillations.

the animal (8), but recent reports have indicated that vasomotion is
not present under more physiological conditions (8–10). Thus, if
anesthesia is very well-controlled in terms of blood pH and blood
gases, vasomotion is not observed (in the tenuissimus muscle),
whereas vasomotion is observed in one-third of animals whose
anesthesia was administered without this precise control (9).
Metabolic acidosis by the infusion of dilute HCl solution induces
vasomotion in most animals. In support of the idea that vasomotion
is not present under physiological conditions, implanted flow
probes in the triceps muscle of awake rabbits under control
conditions failed to report any vasomotion (11). One must thus
conclude that in this vascular bed vasomotion is initiated by
metabolic stress and is absent under resting conditions. This is in
contrast to the early reports on human skin and hamster
subcutaneous muscle, where vasomotion was reported under
conditions that can hardly be denoted as pathological. The problem
with these latter reports is that the prevalence of vasomotion was
not systematically reported, suggesting that vasomotion might have
been present only for brief periods in some of these studies.
Schmidt has critically reviewed the question of whether vasomotion
is present under physiological conditions (11) and reports that
vasomotion is generally most prevalent under conditions of reduced
perfusion. Thus, we may conclude that possibly both the presence
as well as the intensity or quantity of vasomotion is highly variable.
The question of whether vasomotion occurs under normal
conditions or only in circulatory stress is at present being examined.
Oscillations in the diameter or tone of large isolated arteries
have also been observed in vitro with a wide variety of oscillatory
patterns, depending on the invitro technique. Whether such
oscillations should be denoted vasomotion, suggesting a similar
origin as that seen in microcirculation, is a matter of debate.
However, human coronary (12) and pial (13) arteries, canine
subcutaneous arteries (14), rabbit ear small arteries (15), rabbit
mesenteric artery (16), rat basilar artery (17), carotid artery from rat
or dog (18, 19), rat tail artery (20), rat mesenteric small arteries (21),
rat irideal arterioles (22), and many other preparations display some
kind of oscillation in vitro, either spontaneously or when activated
by an agonist (e.g., noradrenaline). These preparations have been
used as models to understand the cellular mechanisms underlying
vasomotion.
NEUROHUMORAL INFLUENCE ON VASOMOTION
In situ oscillations in the vasculature arise from many different
causes. Mechanical oscillations from the movements of the heart and
respiration are most pronounced in veins, but respiratory
movements may confound vasomotion measurements by the laser-
Doppler technique (23). Oscillations in nervous discharges—with
rhythms such as Traube-Hering-Mayer waves (Box 2) having a
periodicity of ten seconds—directly generate oscillations in vascular
tone that could be mistaken for vasomotion. However, because these
oscillations arise from variations in neural discharge, they would be
synchronous in large parts of the body in contrast to true
vasomotion, which is a local phenomenon. Thus, if only a local area
is under study, it becomes difficult to distinguish systemic vascular
oscillations from local oscillations. During measurements of
cutaneous vasomotion in vivo, changes in tone inevitably contribute
to the observed flow changes (24) and possibly are predominant in
larger arteries (25). However, the presence of localized changes in
flow (26) indicates that not all changes in tone are caused by
external signals to the vessels but are generated locally.
Observations on isolated arteries indicate that vasomotion is
enhanced in amplitude and/or frequency by vasoconstricting
receptor agonists. For instance, rat mesenteric small arteries do not

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 Review
Box 2. Blood pressure oscillations: Traube-Hering-Mayer
waves.
In the 19th century, interest began to focus on various
oscillations observed in arterial blood pressure. One began to
talk about oscillations of different order. Order 1, the fastest,
were oscillations due to heartbeat. Order 2 were oscillations due
to the mechanical movements of the chest during respiration.
Order 3 referred mostly to oscillations slower than the other two
and were of unknown origin. However, there were also some
waves of the same frequency as order 2 that could not be
explained as mechanical consequences of breathing.
Traube (98) described in 1865 that if artificial ventilation in a
curarized animal was stopped, blood pressure rose and started to
oscillate at a frequency of about seven rhythms/min (similar to
2nd order oscillations). Similarly Hering (99) in 1869 could
show that if, also in the curarized animal, ventilation was made
rapid and shallow, similar blood pressure waves emerged. In
1876, Mayer (100) reported that in spontaneously breathing
animals, blood pressure oscillations with a frequency lower than
that of respiration appeared if respiration was slightly hindered
(therefore 3rd order waves by definition but actually rather
similar to the Traube and Hering waves). It now appears that all
these oscillations can be ascribed to oscillations in efferent
vasoconstrictor nerve activity, which can be evoked or
exaggerated by cerebral hypercapnia (abnormally high
concentrations of carbon dioxide in the circulating blood).
exhibit vasomotion under basal conditions because of a lack of tone,
but if noradrenaline is administered exogenously, contraction occurs
and oscillations of the contractions develop on top of the induced
tone (21). Such an effect is not limited to noradrenaline, but is
observable in the same assay in the presence of vasopressin or
neuropeptide Y (Gustafsson and Nilsson, unpublished results; see
also 27), as well as other vasoactive peptides (28–30), suggesting it is
primarily a matter of activating the muscle rather than a specific
effect from a certain receptor.
The observations on isolated arteries positively correlate with
observations on the microcirculation in hamster skin-fold
preparations, where adrenergic inhibition reduces, and adrenergic
stimulation enhances, vasomotion (31). The enhancing effects of
systemic hypoxia on vasomotion in this preparation were prevented
by phentolamine (32), indicating that sympathetic tone is a
prerequisite for vasomotion, either by providing a basal level of tone
necessary for oscillation or by stimulating the oscillations directly.
The fact that noradrenaline and other agonists may stimulate
vasomotion might explain the induction of vasomotion by
hemorrhage (8), in that the ensuing sympathetic activation may
provoke vasomotion. Consistently, it has been reported that
inhibiting sympathetic input to the muscle eliminates previously
observed slow-wave vasomotions (11, 33). Furthermore, after
severing the sciatic nerve in rabbits, vasomotion could be induced
in the tenuissimus muscle by stimulation of the nerve, although
82
only when femoral artery pressure was reduced (11). Infusion of
adrenaline, noradrenaline, or vasopressin in this preparation was
similarly capable of eliciting vasomotion at reduced blood pressure
(11). A somewhat different observation comes from Rücker et al.,
who studied vasomotion using controlled perfusion of pedicled
osteomyocutaneous flaps (superficial tissue flaps consisting of skin,
muscle, and bone excised from the animal in such a way that they
are connected only by a narrow stalk through which they obtained
their nerve and blood supply) (34). Although no tissue exhibited
vasomotion under basal conditions, flow reduction did induce
vasomotion in the muscle, irrespective of whether innervation was
intact or not. Thus, the inducing stimulus of vasomotion might be
flow reduction, either in itself or via metabolic changes in the tissue.
However, the sympathetic nervous system might still facilitate
vasomotion, because the neural activity under these experimental
conditions would probably have been low, and removing its
influence would therefore not change the situation significantly.
That nerves are not necessary for oscillations in vascular tone
has also been supported by many studies on isolated arteries. These
are studies where either the generation of action potentials in the
vasomotor nerves (17, 35) or the release or action of the transmitters
(22, 36, 37) have been blocked.
Taken together, these studies seem to indicate that neural
influence is not required for vasomotion to occur. Vasomotion
requires some degree of tone, and if spontaneous tone is not
sufficient, neural or humoral input may elevate tone to a level where
vasomotion may occur. It is also possible that these inputs may
modulate the oscillating mechanism in the vessels, thereby
influencing vasomotion frequency or phase.
In this context it is interesting that vasomotion can be induced
in situations of reactive hyperemia—the increase above baseline in
blood flow after temporary flow obstruction (26)—demonstrating
that tone in arterioles is not fully eliminated by the accumulation of
metabolites during the ischemic period. Furthermore, the upstream
vasodilation that mediates the hyperemia would cause an elevation
of precapillary pressures. Because vasomotion can be triggered by
reduced perfusion, which would cause pressure reduction, it does
not appear likely that it is the acute pressure change itself that is the
stimulus for vasomotion. Conceivably, the accumulation of
metabolites, with ensuing pH changes etc., during the ischemic
period in this situation as well as during hypoperfusion is the
critical event.
ON THE MECHANISM OF VASOMOTION
Vasomotion requires coordination of the activity of the vascular
smooth muscle cells in the vessel wall. There is little doubt that this
is achieved through electrical communication—electrical
communication may be the only means of communication fast
enough to coordinate responses over several millimeters of vessel—
and that oscillations in membrane potential are responsible for the
oscillations in vessel tone. That is, whenever membrane potential

has been measured during vasomotion, the membrane potential
either oscillates with the same frequency as the vasomotion (19, 21,
22, 36) or shows bursts of action potentials in phase with the
tension oscillations (13, 38), and the changes in membrane
potential seem to precede the oscillation in vessel tone (21, 22).
One exception is the observation by Haddock et al. (39), who show
that an oscillating current can be observed in cells in pinned-out
short segments of irideal arterioles under voltage clamp, and under
these conditions “[v]isual observation of the preparation indicated
that rhythmical movements of the preparation continued whilst the
voltage clamp was applied.” It is, however, not clear how such
movements were propagated, and in a further study the authors
suggest a model based on electrical coupling of cells (40).
Further support for the importance of membrane potential
changes in the coupling of cells in vasomotion comes from studies
using gap-junction blockers, which would inhibit vasomotion if
electrical coupling through gap junction was synchronizing cellular
oscillations. This was actually observed by Chaytor et al. (41) who
developed peptides mimicking connexin loops to break
connections between gap-junctional hemichannels. These authors
used the disappearance of vasomotion as an argument for the
peptides’ activity on gap junction; it still remains to be shown
whether these peptides inhibit electrical coupling between cells and
that their effect on vasomotion is not unspecific. It is interesting to
note that another gap-junction inhibitor, 18
-glycyrrhetinic acid,
inhibited both mechanical and electrical oscillations in irideal
arterioles (22)—the effect on electrical oscillations in single cells
suggests either a more profound role for membrane potential
changes in the generation of oscillations or an unspecific effect of
this compound. Another putative gap junction inhibitor, heptanol,
has been shown to have important non-specific effects (42, 43).
It has been suggested that the electrical activity that governs
vasomotion is paced by specific pacemaker cells situated near
bifurcations of blood vessels (44, 45). This concept has been
supported by the demonstration of increased L-type channel density
on the surface of vascular smooth muscle cells and an apparent
spread of the increased [Ca2+]i, as measured by fluorescent
imaging, from branch points to other parts of the vessel following
KCl depolarization (44). On the other hand, there have been very
few reports (46–48) on smooth-muscle-like cells having special
morphological or biophysical characteristics that in the vascular wall
could mediate a pacemaker-like function similar to that of Cajal cells
in the intestine (49). However, Cajal cells were very recently
identified in the portal vein (50), allowing for the intriguing
possibility that some cells in the vessel wall are more likely to
“drive” vasomotion. For such a scenario to be relevant, vasomotion
should originate from the same site in the vasculature or the same
position in an isolated vessel whenever vasomotion is initiated. Due
to the rapid spread (presumably > 1 cm/sec) of the electrical signal,
it is experimentally difficult to determine whether this occurs, and
to our knowledge, it has not been demonstrated. Other studies have
indicated that vasomotion is unlikely to start from a fixed
Smooth muscle oscillations
pacemaker (51, 52).
An alternative possibility is that coordination occurs through
entrainment of smooth muscle cells oscillating asynchronously. In
other words, it is possible that all or nearly all vascular smooth-
muscle cells may be able to oscillate and, through interconnections,
eventually entrain. With this scheme it will be of interest to: a)
understand the mechanism responsible for the oscillation in the
individual cell and b) understand how the coupling of the cells
leads to entrainment.
An intriguing possibility for an oscillating mechanism was
suggested by Siegel (19) and is based on oscillations in
phosphofructokinase-1 activity leading to oscillations in ATP and,
consequently, oscillations in Na+, K+–ATPase (or Na+ pump)
activity. The electrogenic nature of the Na+ pump would lead to
oscillations in membrane potential, which could spread to
neighboring cells. This suggestion is supported by the observation
of several authors that ouabain-mediated inhibition of the Na+
pump blocks vasomotion (35, 53–56). How the Na+ pumps of
individual cells are entrained in this model to effect synchronized
vasomotion in larger areas has, however, not been discussed.
Several authors have suggested that the sarcoplasmic
reticulum (SR) is important for vasomotion (22, 56–59). Different
blockers of the SR Ca2+-pump (SERCA) inhibit vasomotion, and
the interaction of an oscillator whose activity is mediated by the SR
and the sarcolemma of smooth muscle cells has been suggested (51,
58, 60). We have hypothesized (36) that the unsynchronized waves
of Ca2+ reported in several smooth muscle cells—both isolated
cells (61, 62) and in the intact arterial wall (36, 62–64)—might
constitute a basal oscillator, which, through cooperation with the
sarcolemma, leads to membrane potential oscillation and
consequent synchronization of smooth muscle cells in the vascular
wall (Figure 1). Recently, Haddock and Hill (40) proposed a model
based on similar principles (calcium release from intracellular
stores synchronized by a calcium-dependent chloride current) to
account for vasomotion in irideal arterioles.
Another important element in the mechanism responsible for
vasomotion is the endothelium–nitric oxide (NO)–cGMP axis
(Figure 2). Although little evidence has been obtained from in vivo
investigations (65, 66), several authors have assessed the role of
these elements for vasomotion under in vitro conditions. Strikingly,
the reports differ quite substantially, and although NO prevents
vasomotion in some arteries (22, 67), NO enhances the prevalence
of vasomotion in other vessels (21, 37). An understanding of the
reason for this variable effect may bring us closer to an
understanding of the mechanisms involved in vasomotion.
In regard to the role of NO in enhancing vasomotion, we have
recenty discovered a cGMP-dependent, Ca2+-activated chloride
channel (Matchkov, Aalkjær, and Nilsson, unpublished results).
This channel appears responsible for coupling the Ca2+ oscillations
generated by the SR to the membrane current that synchronizes
individual cells. We hypothesize that NO levels could elevate cGMP
concentrations in smooth muscle cells, thereby increasing the
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 Review
likelihood of synchronized oscillation. At the same time, other
effects of NO may be inhibitory on the SR oscillator (68) by
modulating intracellular calcium availability, uptake, and/or release.
Thus, an NO–cGMP system might regulate vasomotion both
through the generation of oscillation and cellular coupling.
FUNCTIONAL CONSEQUENCES OF VASOMOTION
There is very little data concerning the physiological function of
vasomotion. It is conceivable that vasomotion is merely a harmless
consequence of smooth-muscle contraction, oscillating under
particular conditions, that has not been eliminated during
evolution. Flow oscillation might arise from oscillations based on
the phase delay in the myogenic response (69); if the response of a
blood vessel to a pressure change comes with a delay, a brief
pressure pulse may start an oscillation in vessel tone. On the other
hand, vasomotion may be beneficial under certain conditions. A
vessel with an oscillating diameter has higher conductance (and
therefore greater flow) than a vessel with a constant diameter of the
same average width (70). An oscillating contraction might be less
costly in terms of energy usage than a constant contraction, but
experimental data supporting such a view are scarce. Along similar
lines, one could argue that by constantly varying its state of
contraction, the vascular muscle does not enter the “latch state” of
contraction. (The latch state, characteristic of many smooth
muscles, is a state of low contraction velocity combined with low
ATPase activity, enabling the muscle to maintain contraction with
low energy expenditure at the expense of the ability to shorten
rapidly). On the other hand, avoidance of the latch state might
confer the advantage that the muscle remains able to shorten
rapidly, thereby capable of responding quickly to neurogenic
commands.
One of the most interesting suggestions is that vasomotion is
beneficial for tissue oxygenation, especially in situations where
perfusion is critically limited. The foundation for this idea comes
from theoretical modeling by Tsai and Intaglietta (71) that suggests
that periods of high flow at low frequency of oscillation, such as
during the slow-wave vasomotion typical for proximal arterioles,
permit long-distance diffusion of oxygen to capillaries; thus, at
critical perfusion levels, oxygen becomes more homogeneously
distributed, and less of the tissue is exposed to very low levels of
oxygen. However, the recent theoretical analysis by Goldman and
Popel (72) argued that vasomotion could promote tissue
oxygenation only at low concentrations of myoglobin, suggesting
that vasomotion would have limited influence on muscle
oxygenation. To address the relation of vasomotion to tissue
oxygenation, Rücker et al. (73) studied perfused rat hindlimbs by
intravital microscopy and used NADH fluorescence as an indication
of the metabolic state of the tissues. When perfusion was reduced,
vasomotion was induced in most muscle preparations. By
comparing preparations with and without vasomotion, the authors
concluded that vasomotion enhanced blood flow to adjacent tissues
84
Figure 2. The endothelium–NO–cGMP axis. Stimulation of
the endothelium, either by receptor agonists such as acetylcholine
(ACh) or by mechanical forces, activates endothelial nitric oxide
synthase (eNOS). This may occur by calcium-dependent and
calcium-independent pathways, some of which are indicated here.
Calcium elevation may be caused by release from stores or by
influx through calcium-permeable pathways [e.g., transient receptor
potential (TRP) channels] activated as a consequence of store
depletion; the mechanism by which store depletion activates influx
is subject to intense study. Calcium-independent pathways involve
the activation of various kinases. Activated eNOS catalyzes the
conversion of L-arginine to citrulline and nitric oxide (NO), which
diffuses to the smooth muscle where it activates soluble guanylate
cyclase (sGC), converting GTP to cyclic GMP (cGMP). In the
smooth muscle, cGMP has a multitude of effects that comprise
activation of myosin light-chain phosphatase (MLCP) causing
desensitization to intracellular calcium of the contractile machinery,
probably activating the sarcoplasmic reticulum calcium ATPase
(SERCA) and the plasma membrane calcium ATPase (PMCA),
opening of K+ channels, and, as suggested by our recent
experiments, enabling a calcium-activated Cl– channel. Many of
these effects are mediated by activation of protein kinase G (PKG).
Most effects of NO on the smooth muscle inhibit contraction; the
Cl– channel, which causes depolarization and thus promotes
contraction, we suggest is responsible for superimposed intermittent
contractions responsible for vasomotion. PKB, protein kinase B
(Akt); PKC, protein kinase C; FAK, focal adhesion kinase.
(e.g., skin, subcutis, and periosteum) and maintained high NADH
fluorescence in the tissues adjacent to muscle, suggesting a
beneficial effect on oxygenation in adjacent tissues. Thus,
vasomotion may be of little importance to muscle (with a high
cellular buffering capacity for oxygen) but of greater importance for
other tissues. This result seemingly suggests that flow is diverted
from the muscle to the other tissues, which is not consistent with
that fact that vasomotion by itself reduces flow resistance; but the
results could imply that when vasomotion is present, artery tone is
higher in the muscle than when it was absent.
 Smooth muscle oscillations

Some theoretical models (71, 74) have been constructed
regarding the role of vasomotion in capillary function, particularly
in the maintenance of both low interstitial pressure and contancy of
paracapillary fluid flux. These models have so far not given
unanimous predictions, but it seems clear that vasomotion may
strongly influence capillary exchange. Unfortunately, the
conclusions borne from theoretical studies have received little
direct support from experiments (71, 74).
PATHOPHYSIOLOGICAL ROLE OF VASOMOTION
There is evidence that the prevalence of vasomotion may be altered
under pathophysiological conditions. In diabetes there is good
evidence that vasomotion is less prevalent. Stansberry et al. (75)
found that in insulin-dependent and in insulin-independent
diabetics the amplitude of vasomotion in the finger was reduced to
about 20%, and the authors concluded that vasomotion was
impaired in 75% of diabetics. In the skin of the feet of diabetic
patients with neuropathy, but not in diabetics without neuropathy,
the amplitude of flow-motion is also reduced (76). These
observations are in accordance with a number of animal studies
showing that in streptozotocin-induced diabetes, vasomotion
essentially disappears in bat wings (77), hamster cheek pouch (78),
and rat spinotrapezius muscle (79) in vivo. Renaudin et al. reported
that acute infusion of glucose to rats increased the prevalence of
vasomotion in the spinotrapezius muscle (79). We are unaware
whether any research has addressed the pathophysiology of
vasomotion under in vitro conditions.
Metformin, the biguanide that is used to treat non-insulin-
dependent diabetes, increases the prevalence of vasomotion.
Intravenous injection of metformin into hamster cheek pouches
acutely induces vasomotion (80), and vasomotion reappears in the
wings of diabetic bats treated with metformin (77). Also, in
anesthetized hamsters exposed to hemorrhagic shock, injection of
metformin acutely induced vasomotion (81). Similarly, in mildly
hyperglycemic animals (streptozotocin treated), injections of
metformin prevented insulin-induced inhibition of vasomotion
(78). As for the studies on diabetes, there are no reports on the
effect of metformin in isolated arteries, and the reason for this effect
of metformin is entirely unknown.
Increased prevalence of vasomotion has been extensively
studied in hypertension. Enhanced vasomotion has been observed
in femoral arteries from renal hypertensive rats (82),
deoxycorticosterone acetate– (DOCA)–salt hypertensive rats (83),
and in rats genetically predisposed to hypertension (35, 38, 83–87).
Interestingly, studies in cross-bred genetic hypertensive and
normotensive rats (88, 89) show that the prevalence of increased
vasomotion positively correlates with increased blood pressure,
indicating a tight coupling between high blood pressure and the
ability to oscillate. These findings, together with the observation that
vasomotion seems to be less prevalent in hypertensive rats treated
with ACE inhibitors (90, 91), seem to indicate that high blood
pressure evoked through several different mechanisms may induce
the oscillations. Thus, in contrast to acute pressure changes, a
chronically elevated pressure level apparently promotes vasomotion.
One could thus speculate that the capillary rarefaction seen in the
hypertensive vasculature (92) could be ameliorated by vasomotive
oxygen delivery (see above). Although an in vivo study of renal
hypertensive rats reveals periods of relative vasoconstriction and
vasodilation in the cremaster muscle (93), this pattern of contraction
and dilation is not similar to what is normally reported for
vasomotion. Nevertheless, in essential hypertensive patients,
Hollenberg and coworkers (94, 95) observed increased amplitude in
vasomotion per se. There is also some in vitro evidence for
enhanced vasomotion in human hypertension: isolated arteries from
women with preeclampsia exhibit more vasomotion than is
observed in arteries from normotensive pregnant women (96, 97).
CONCLUSION
Vasomotion, in the restricted sense of the word, denotes oscillations
in vascular tone. These oscillations can occur in vessels in many
tissues in vivo, and correlates can be seen in vitro in isolated
preparations of arteries. The in vitro approach enables us to study the
mechanisms underlying oscillations in multicellular tissues, but the
connection between these generally relatively large preparations and
the oscillations in terminal arterioles seen in vivo remains to be
determined. In spite of a large body of experimental work, the
physiological significance of vasomotion remains elusive. Arguably,
there is some evidence pointing in the direction of a role in tissue
oxygenation when perfusion is compromised. If so, the phenomenon
would be a mechanism of substantial pathophysiological importance.
Although vasomotion has been like the weather—many talk about it
but few do anything seriously about it—we have begun to unravel
the cellular and molecular mechanisms of oscillation and cellular
coupling underlying vasomotion.

References
1. Jones, T.W. Discovery that the veins
of the bat’s wing are endowed with
rhythmical contractility and that
onward flow of blood is accelerated
by each contraction. Phil. Trans. Roy.
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