480
Histamine-Induced Rhythmic Contraction of Hog
Carotid Artery Smooth Muscle
Philip G. Stein and Steven P. Driska
From the Department of Physiology and Biophysics, Medical College of Virginia, Virginia Commonwealth University,
Richmond, Virginia
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SUMMARY. Smooth muscle strips isolated from the hog common carotid artery can contract
rhythmically, exhibiting low frequency, large amplitude oscillations in tension when stimulated
with 10 IIM histamine. Strips required at least 1.45 ITIM calcium and 2.5 mM potassium to exhibit
this rhythmic activity. Rhythmic contractions could be converted to tonic contractions by removal
of potassium or ouabain treatment. Relaxation by 2 mM lanthanum, 1 mM manganese, or 1 fiM
verapamil implies that the external medium is the source of calcium mediating the contractions.
The involvement of adrenergic nerve terminals in this response was ruled out, since propranolol,
phentolamine, tetrodotoxin, bretylium, or 6-hydroxydopamine treatment did not alter the oscillations. Blockade of H! receptors with 0.1 HM diphenhydramine relaxed the muscle strips. The H2
receptor antagonist cimetidine (5 fiM) had no effects. Attempts to obtain rhythmic contractions by
stimulating with other vasoactive agents (norepinephrine, acetylcholine, 5-hydroxytryptamine,
angiotensin II, and elevated potassium concentrations) were unsuccessful, suggesting that this is
a specific histamine response mediated solely by Hi receptors. These results show that this large
artery, commonly considered a multi-unit smooth muscle, can sometimes exhibit single-unit
behavior. (CircRes 55: 480-485, 1984)
SMOOTH muscle is often classified according to its
functional characteristics as either single-unit or
multi-unit (Bozler, 1941). Large arteries, including
the hog carotid, are considered to be good examples
of multi-unit smooth muscle. This type of smooth
muscle is characterized by the lack of myogenic and
rhythmic activity, the presence of very few gap
junctions, the inability to propagate electrical activity, and the ability to respond to excitatory stimuli
with only graded, tonic contractions (Somlyo and
Somlyo, 1968a, 1968b). Recently we found that
histamine stimulation can make the hog carotid
artery contract rhythmically, an ability that apparently conflicts with the multi-unit classification. This
is interesting because the effect is dose-dependent;
at high concentrations, histamine contractions are
tonic, as expected for a multi-unit muscle.
There are some reports of rhythmic contraction of
other multi-unit smooth muscles in the recent literature. Only a few of these reports describe regular,
large amplitude rhythmic contractions in most of
the tissues studied (Biamino and Kruckenberg, 1969;
Ross et al., 1980; Ginsburg et al., 1980; Bose and
Bose, 1977). Many of these instances of rhythmic
contraction may result from pathological states (Bandick and Sparks, 1970; Bohr and Sitrin, 1970; Ginsburg et al., 1980; Ross et al., 1980; Golenhofen et
al., 1981; Ueda et al., 1981) or deliberately nonphysiological conditions (Bose and Bose, 1977; Kannan
and Daniel, 1978). Also, in some of these studies,
the rhythmic component of force was small and
superimposed on a much stronger tonic contraction
(Johansson and Bohr, 1966; Bevan and Ljung, 1974)
or the rhythmic contractions were noted only occasionally (Barr et al., 1962; Norton and Detar, 1972)
or during equilibration at 37°C after cold storage
(Barr et al., 1962).
In contrast, the rhythmic contractions we report
here are strong, with only a small tonic component
of force; they are demonstrable in a large fraction
(75%) of the arteries tested; they occur with tissue
from normal animals; and they result from stimulation by a physiologically occurring agonist. The
simple conditions required to elicit this response, its
reproducibility, and the large amplitude of the contractions, suggest that this may be a fundamental
property of large artery smooth muscle that has
received little attention. The experiments reported
here were undertaken to characterize this response.
Methods
Common carotid arteries were collected from 100- to
400-kg swine of either sex, at slaughter. Any thrombi in
the vessels were rinsed out, and the arteries were placed
in 0°C physiological saline solution (PSS) of the following
composition (in mM): NaCl, 117.8; NaH2PO4, 1.2;
Na2EDTA, 0.027; KC1, 6.0; CaCl2, 1.6; MgSO4, 1.2; NaHCO3, 24.3; and glucose, 5.6. Gassed with 95% O2, 5%
CO2, this PSS has a pH of 7.4 at 37°C. Arteries stored in
this PSS at 4°C remain viable for 2-3 days. The minimum
time from the death of the animals to mounting of a strip
in the muscle bath was about 3 hours.
Medial-intimal strips were prepared as described pre-
Stein and Driska/Rhythmic Contraction of Arterial Smooth Muscle
viously (Driska et al., 1981). Strips were blotted for approximately 10 seconds on absorbent paper and weighed
before the experiments. Strips which were not blotted and
weighed were also capable of contracting rhythmically.
Strips 2-3 mm wide were mounted with stainless steel
clips to an apparatus which allowed strip length to be
measured and changed with a resolution of 0.1 mm. Force
was measured with Grass FT.03C transducers and recorded on Grass or Beckman recorders. The total mechanical compliance of this apparatus was 5 fim/g. Strips were
immersed in 50 ml of 37°C PSS which was gassed continuously with 95% O2, 5% CO2. Strips were then stretched
in one motion to a length yielding 10 g tension and
allowed to equilibrate for at least 1 hour or until tension
returned to baseline.
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Dose-Response Curves
Normalized dose-response curves for tonic active force
in response to histamine were constructed and the data
for six tissues averaged. The ED50 value was determined
from the mean data by linear regression analysis using the
equation log10 (F/(Fmax-F)) = log10D - logi0ED50. Here, F
represents the force elicited by a given dose (D) of histamine, and Fmax represents the maximum force obtained
(with 30 /iM histamine). The slope of the fitted line was
1.85, the correlation coefficient was 0.995, and the ED50
was 3.4 JIM. Dose-response curves in the presence of 20
HM cimetidine were identical to those obtained in its absence.
Solutions
Length-tension relationships were determined (Herlihy
and Murphy, 1973), using K+ PSS stimulation. The K+
PSS had the same composition as the PSS described
above, except for an equimolar substitution of KG for
NaCl. Experiments involving La+++ and Mn++ required
the use of a saline solution of the following composition
(in HIM): NaCl, 140; MgSO4, 1.2; CaCl2, 1.6; KC1, 6; Dglucose, 5.6; and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), 5.0 Gassed with 100% O2, this
PSS had a pH of 7.45 at 37°C. Histamine dihydrochloride
(HA), norepinephrine (NE), 6-hydroxydopamine, tetrodotoxin (TTX), ouabain, acetylcholine (ACh), and 5-hydroxytryptamine (5-HT) were purchased from Sigma. Tetraethylammonium chloride (TEA) and 4-aminopyridine
(4-AP) were purchased from Aldrich. Verapamil was a
gift of Knoll Laboratories, and Smith, Kline, and French
donated the 2-methylhistamine and 4-methylhistamine.
Statistical Analysis
Means, ranges, and standard deviations were used to
express the variability of the oscillations in different strips
with respect to latency, amplitude, and frequency. In a
preliminary report (Stein and Driska, 1981), 128 (75%) of
the 172 strips tested showed oscillations; since that time,
the total number of strips has increased to several hundred
with about the same percentage showing oscillations. In
studies of agents which inhibited rhythmic contractions,
inhibition was defined as a decrease of over 90% in the
amplitude of the force oscillations. Because strips sometimes stopped contracting rhythmically and relaxed spontaneously, it was important to estimate the probability that
the oscillations stopped by coincidence rather than as a
result of the intervention. In the data presented for inhbitory agents, the number of strips tested (n) is given, and
each test had a successful result. The probabilities of these
481
results being coincidences were computed using the binomial distribution, assuming equal chances of a result
being due to coincidence or being due to the intervention.
Thus, the probability of the results due to chance is {Vi)",
or 0.125 for n = 3, 0.0625 for n = 4, 0.031 for n = 5, 0.016
for n = 6, and 0.008 for n = 7. In experiments in which
no effect of an agent was found, the number of experiments, n, was between 3 and 6, unless otherwise noted.
Results
Mechanical Characteristics of the Contractions
When hog carotid artery smooth muscle strips are
stimulated with 10 ^M HA, most (75%) exhibit the
response seen in Figure 1. The general response is a
tonic contraction of variable duration (2 to 30 minutes, mean = 14 min) which then develops rhythmicity, i.e., oscillations in force. Fifteen to 30 minutes
after the onset of oscillations, the force excursions
reach a maximum with a fairly constant amplitude
and frequency (range: 7.5 to 43/hr, or periods of
1.4-8 minutes). Whereas the frequency is fairly constant for a given tissue, there is much variation
between tissues.
The rhythmic component of contraction is strong;
it is not simply a small tension fluctuation superimposed on a strong tonic contraction. In a random
sample of 25 of the arteries studied, the peak
rhythmic force was 116.0 ± 51% (SD) of the tonic
force produced by histamine. The force decreased
to 36.9 ± 1 1 % (SD) of the tonic histamine force (or
32% of the peak force) during the relaxation phase,
although in some cases relaxation was more complete (<10% of tonic force). Strips continued contracting in this fashion for up to 6 hours. When
rhythmic activity stopped, most strips began to relax
progressively less between force peaks, eventually
developing a tonic contraction.
Histamine concentrations between 5 and 10 MM
routinely produced rhythmic contractions. On occasion, concentrations as low as 8 X 10~7 M and as
high as 4 X 10~5 M produced oscillations. Concentrations that were too high produced strong tonic
contractions. Dose-response curves of tonic contractile force with HA stimulation (not shown) have an
50 -1
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10
20
30
40
50
60
MINUTES
FIGURE 1. Typical response to stimulation with 10 /JM histamine.
Histamine was added to the bath at the beginning of the time scale.
Before stimulation, the muscle was completely relaxed and there was
no active or passive tension. After 10 minutes of stimulation, oscillations (with a period of about 2 minutes) began. Note that the force
of the rhythmic contractions exceeded the original tonic force measured before rhythmicity developed. Recordings of isometric force were
made with a curvilinear (Grass) recorder.
Circulation Research/Vol. 55, No. 4, October 1984
482
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ED50 of 3.4 /*M, and 10 /XM histamine elicits 88% of
the maximum tonic force. Since rhythmic contractions did not usually occur at higher HA concentrations, it seems that full occupancy of histamine
receptors is incompatible with rhythmic activity.
Strips were routinely stretched to reach 10 g force
when first mounted in the apparatus, and experiments were done at the length determined by this
stretch. Length-tension curves constructed at the
end of some experiments determined that the 10 g
stretch resulted in a strip length of 0.63 ± 0.04 U
where Lo is the optimal length for force development. At 0.63 Lo, active stress with 10 (J.M HA
stimulation is 1.39 ± 0.24 X 105 N/m 2 (SD, n = 25),
which is about the same as that with K+ PSS.
Arteries were routinely transported in 0°C PSS,
but on one occasion we collected and transported
arteries to the laboratory in warm (29-33°C) PSS.
Two muscle strips from each of six arteries were
studied; of these 12 strips, six contracted rhythmically. This shows that rhythmicity was not a consequence of cold storage of the arteries.
Involvement of Nerve Terminals
It has been reported that the swine carotid artery
cannot propagate electrical activity (Burnstock and
Prosser,1960). An alternate mechanism for synchronizing contractions in a tissue incapable of propagated electrical activity would be through synchronized release of norepinephrine from the network
of adrenergic nerve endings in the preparation. Several experiments designed to test for such a mechanism failed to produce evidence for nerve terminal
involvement.
Tetrodotoxin (TTX), by blocking fast Na+ channels
in adrenergic nerves, should block both conduction
along a nerve network and release of NE from nerve
terminals mediated by action potentials. However,
1 HM TTX did not affect the rhythmic contractile
activity. Neither 10 fiu bretylium tosylate (a blocker
of norepinephrine release) nor 10 fiM phentolamine
(an a-adrenergic receptor blocker) had any effects
on the force oscillations. DL-propranolol (10 /IM) also
had no effect, which rules out the possibility of /?receptors mediating the relaxation phase of the
rhythmic contractions. Finally, treatment of the
strips with 6-hydroxydopamine to destroy adrenergic nerve terminals (Aprigliano and Hermsmeyer,
1976) did not prevent rhythmic contractions when
strips were later stimulated with histamine (n = 7).
These experiments rule out rhythmic synchronized
NE release from nerve terminals as the cause of the
rhythmicity of the contractions.
cells which are likely to be the site of prostaglandin
generation. Exposure of the strips to 80 H*A indomethacin (a prostaglandin synthesis inhibitor) for
20 minutes prior to histamine stimulation had no
effect on the oscillations, nor did indomethacin
when it was added during the oscillations (n = 3).
These facts suggest that prostaglandin formation is
not involved in the rhythmicity.
Histamine Receptor Studies
Both H]- and H2-histamine receptors are present
in the vasculature, and one possible explanation for
the oscillations was that one type of histamine receptor was responsible for the contraction and the
other for the relaxation. The addition of 0.1 MM
diphenhydramine, an Hi antagonist, caused rapid
and complete relaxation, as shown in Figure 2 (n =
5). When 10 ^M HA was replaced by the Hi agonist,
2-methylhistamine (10 IXM), the rhythmic contractions were unchanged (« = 4), confirming that Hi
receptors are responsible for the oscillations. Cimetidine (5 HM), an H2 antagonist, had no effect. Addition of 10 /XM 4-methylhistamine (an H2 specific
agonist) to strips stimulated by either HA or 2methylhistamine had no effect. As expected, 4methylhistamine alone did not cause the strips to
contract (n = 4). These results show that activation
through Hi receptors alone is sufficient to generate
rhythmic activity, and that H2 receptors do not have
a role in the response.
Ionic Requirements
The Ca++ concentration in the bathing medium
has a marked effect on oscillatory activity. Addition
of 1.6 mM EGTA to the normal PSS (1.6 HIM Ca++)
or substitution of the normal PSS with one nominally free of Ca++ stopped the oscillations (n = 5).
CaCl2 was added back to the tissue baths in 0.2 mM
increments to determine the [Ca++] threshold for
resumption of oscillations, which was 1.45 mM ±
0.18 (SD, n = 8).
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Prostaglandins
Prostaglandins have recently been implicated in
the rhythmic contraction of human renal artery
strips (Ueda et al., 1981). We routinely blotted the
muscle strips with filter paper for weighing before
the experiments, and this destroys the endothelial
-10
10
MINUTES
FIGURE 2. Relaxation by histamine H, receptor blockade. Diphenhydramine was added to give a bath concentration of J0~7 M. The time
scale is aligned so that zero corresponds to the time that diphenhydramine was added. The histamine concentration was I0~5 M throughout.
483
Stein and Driska/Rhythmic Contraction of Arterial Smooth Muscle
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Transmembrane Ca++ flux appears to be necessary for oscillations. Blockade of the slow channels
with 2 mM La+++ (n = 7), 1 rrtM Mn++ (« = 6), or 1
fiM verapamil (n = 4) (all in the presence of 1.6 mM
CaCl2) rapidly stopped the oscillations and relaxed
the smooth muscle. The ability of verapamil to block
the contractions suggests that it is the entry of Ca++
into the cell (rather than the binding of Ca++ to sites
in the tissue or 'stabilization* of the membrane) that
is required for the rhythmic contractions.
Potassium was also required for the rhythmic
response. If muscle strips were incubated in K+-free
PSS for 20 minutes, HA produced only tonic contractions on stimulation (n = 20). When rhythmically
contracting strips in normal PSS were switched to a
K+-free PSS containing 10 MM HA, the rhythmic
contractions were converted to a tonic contraction.
Rhythmicity could be restored by the reintroduction
of K+ to the bath (n = 7), as shown in Figure 3.
When K+ was introduced in 0.2 mM increments,
oscillations reappeared when K+ reached a mean
value of 2.5 ± 0.62 mM (SD, n = 7). Elevation of [K+]
to 30 HIM produced sustained contractures.
Ouabain
Ouabain (1 MM) rapidly converted the rhythmic
contractions of the strips to sustained contractures
(Fig. 4, n = 4). This shows that Na-K pump activity
is required either in a direct way as a pacemaker or
indirectly in maintaining membrane potential and/
or concentration gradients in specific ranges.
0
30
60
90
120
MINUTES
FIGURE 3. [K]o dependence of oscillatory contractions. Stimulation
with 10 HM HA began at zero minutes and continued for the entire
experiment. The bathing medium was replaced with K*-free PSS +
10 (/M HA at the point indicated by the first arrow, converting the
oscillations to a tonic contraction. Additions of KCl to give 2 mM
increments are denoted by each successive arrow. Bath K* concentration is shown above the force record.
Other Vasoactive Agents
To determine whether the rhythmic contractions
were specific for histamine, we attempted to elicit
rhythmic contractions using the following vasoac50 -i
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0
30
60
90
MINUTES
FIGURE 4. Effect of ouabain on rhythmic contraction. Ouabain (1(T6
M) added to the bath at the arrow abruptly stopped the oscillations.
Stimulation with 10 HMHA began at zero minutes.
5O-i
0
J
30
60
90
MINUTES
FIGURE 5. Contractions produced by TEA. TEA (4 DIM) was added to
the bath at zero minutes. No histamine had been added to the bath.
Compare to the regular, more sinusoidal records obtained with histamine stimulation in Figure 1.
rive agents: NE (1-100 MM, n = 13), ACh (100-1000
MM, n = 13), 5-HT (1-10 MM, n = 13), K+ elevation
(15 mM, 20 HIM, n = 11), angiotensin-II (1-10 MM, n
= 4), TEA (4-8 HIM), and 4-AP (2 mM). Of these
agents, the two potassium conductance blockers, 4AP and TEA, were the only ones to elicit any type
of rhythmic contractile activity. TEA and 4-AP always (n = 7) produced a train of rhythmic contractions, less sinusoidal than those caused by HA and
less regular in frequency, usually with a more rapid
development of tension. An example is shown in
Figure 5. It is not known if the rhythmic contractions
caused by TEA and histamine occur by similar or
different mechanisms. Neither arropine (1 MM nor
methysergide (10 MM) had any effect on histamineinduced oscillations, which suggests that cholinergic
and serotonergic receptors are not involved.
Glucose Deprivation
Glucose deprivation causes rhythmic activity in
dog trachealis (Bose and Bose, 1977). However, with
the hog carotid, the amplitude, frequency, and duration of the rhythmic contractions were the same
at three different glucose concentrations (0, 5.6, and
15.6 mM, n = 6). This shows that the rhythmic
contractions do not arise from a deficiency of glucose
in the bathing medium.
Discussion
It is appropriate to consider possibilities which
could artifactually cause the behavior reported here.
Some of these possibilities are listed below. Arteries
were routinely flushed with cold PSS at the slaughterhouse to remove blood or thrombi. Rhythmic
contractions were also exhibited in experiments in
which only arteries free of thrombi were collected,
so it did not appear that the oscillations were due to
prior exposure of the blood vessels to thrombi. Cooling arteries to 0°C in PSS for transport, dissection,
and storage is a common procedure, but it raises
questions of possible alterations in function, especially with regard to receptors and the integrity of
nerve endings in the preparation. Cold storage also
causes loss of K+ from cells and accumulation of
Na+, a situation that results in strongly elecrrogenic
Na+ extrusion on warming. Such a mechanism was
suggested for the rhythmicity occasionally observed
in dog carotid artery strips warming after cold stor-
484
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age (Barr et al., 1962). We do not think that prior
cold storage is the explanation for the oscillations
reported here for the following reasons: (1) strips
were allowed to equilibrate for 2 hours at 37°C
before stimulation with HA; (2) histamine also
caused rhythmic contractions in strips which had
been stimulated repeatedly with K+ PSS over a
period of hours, showing that rhythmicity is not an
artifact restricted to the first contraction at 37°C;
and (3) strips from arteries that were collected and
transported to the laboratory in warm PSS also
contracted rhythmically in 10 fiM HA.
The rhythmic mechanical activity implies that
there must be both a pacemaker and a means of
coordinating the responses of the individual cells.
By using blockers of NE release, blockers of adrenergic receptors and, finally, 6-hydroxydopamine
treatment to destroy the nerve terminals, we have
shown that the adrenergic nerve terminals cannot
be the pacemaker or the means for coordinating the
muscle cell response. This suggests that smooth
muscle cells are the source of the rhythmicity. These
results also imply some mechanism for coordinating
cells in the tissue, yet this conflicts with the finding
that there is no conduction in the hog carotid (Burnstock and Prosser, 1960). One explanation for this
apparent conflict is that the carotid artery might
conduct electrical activity only when exposed to
histamine or other contractile agonists.
Histamine stimulation of arterial smooth muscle
usually causes an initial rapid phase of contraction
thought to correspond to the release of Ca++ from
internal stores, and a slower tonic phase thought to
reflect the entry of Ca++ from the extracellular space
(Hudgins and Weiss, 1968; Watkins and Davidson,
1980). The sources and sinks for the Ca++ ions
involved in the rhythmic contractions are not
known, but the experiments with La+++, Mn++ and
verapamil indicate that influx of extracellular Ca++
is required. Histamine has been shown to increase
Ca++ permeability in other arterial smooth muscles
(Harder, 1980). However, this does not rule out
participation by intracellular Ca ++ pools, e.g., Ca++induced Ca++ release from the sarcoplasmic reticulum. The necessity of extracellular calcium for the
rhythmic contractions suggests that the contraction
amplitude would depend on [Ca++]o. However, a
simple monotonic relationship between peak force
and [Ca++]o was not found (unpublished results).
Histamine-induced contractions did not show
rhythmicity when the K+ concentration of the bathing solution, [K+]o, was less than 1.2 ITIM. Potassium-free solutions usually depolarize vascular
smooth muscle, whether through inhibition of an
electrogenic Na-K pump, a decrease in potassium
conductance, or indirectly, through norepinephrine
release from nerve endings (for a review, see Hermsmeyer, 1983). Such a depolarization might prevent
rhythmicity. The [K+]o requirement for rhythmicity
could also arise through its role in Na-K pump
Circulation Research/Vol. 55, No. 4, October 1984
activation or through mechanisms involving
rhythmic conductance changes. The most likely
interpretation of this K+ requirement is that the
electrogenic Na-K pump in the smooth muscle membrane must be operating for the rhythmic behavior
to develop. Relaxation of vascular smooth muscle
following the reintroduction of K+ to a K+-deficient
bathing medium is thought, by some authors, to be
due solely to the stimulation of the electrogenic NaK pump and the concomitant hyperpolarization of
the membrane (Biamino and Wessel, 1973; Hendrickx and Casteels, 1974; Webb and Bohr, 1978;
Hermsmeyer, 1983). The fact that ouabain rapidly
stops the oscillations and causes a tonic contracture
is another indicator that the activity of the Na+,K+ATPase is a necessary component of the relaxation
phase of this phenomenon. The effect of ouabain is
rapid enough in these experiments (less than 1 minute in Fig. 4) that it probably is due to a loss of an
electrogenic component of membrane potential,
rather than to other consequences of ouabain treatment, such as Na + accumulation or K+ depletion.
Rhythmic contractions are often considered an
unusual response for a multi-unit tissue like the hog
carotid artery. However, there have been reports of
similar behavior in other multi-unit tissues in the
recent literature (see introduction), and in the early
1900's there were a few reports of large arteries
showing single-unit properties like rhythmic contraction and myogenic responses. These results came
from several arterial tissues; dog carotid (Bayliss,
1902), cow renal and mesenteric (Rothlin, 1920),
horse carotid (Wachholder, 1921), and cow carotid
(Full, 1913; Miiller, 1906). We do not mean to suggest that the hog carotid artery is really a single-unit
smooth muscle, nor do we advocate discarding the
single-unit/multi-unit classification system. The major point we wish to emphasize is that, under certain
experimental conditions, multi-unit tissues like the
hog carotid artery can exhibit single-unit behavior.
It is not known whether this unusual behavior is
related to the rhythmic contractions sometimes seen
in pathological arteries. Even though it is probably
an oversimplification, the classification of smooth
muscle as either single-unit or multi-unit has been
very useful in our understanding of smooth muscle
physiology over the years. With the understanding
that such a classification might not be true under all
conditions, this concept should still provide a useful
framework for smooth muscle research in the future.
Supported by National Institutes of Health Grants HL 24881 and
HL 25383. S.P. Driska is the recipient of National Institutes of Health
Research Career Development Award HL 01198.
Dr. Stein's current address is: C.V. Whitney Laboratory, University
of Florida, Rt. 1, Box 121, St. Augustine, Florida 32086.
Address for reprints: Dr. S.P. Driska, Department of Physiology
and Biophysics, Medical College of Virginia, Box 551, MCV Station,
Richmond, Virginia 23298.
Received June 17, 1982; revised manuscript received December 28,
1983; accepted for publication July II, 1984.
Stein and Drisfca/Rhythmic Contraction of Arterial Smooth Muscle
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INDEX TERMS: Rhythmic contraction • Hog carotid artery •
Histamine • Vascular smooth muscle
Histamine-induced rhythmic contraction of hog carotid artery smooth muscle.
P G Stein and S P Driska
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Circ Res. 1984;55:480-485
doi: 10.1161/01.RES.55.4.480
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