From the Department of Surgery, Division of Vascular Surgery, Oregon
Health Sciences University, Portland (M.J.C.) and Department of Obstetrics and
Gynecology, University of Vermont College of Medicine, Burlington (G.O.).
Correspondence to Marilyn J. Cipolla, PhD, Division of Vascular Surgery, OP-11, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail cipollam{at}ohsu.edu
Methods—Posterior cerebral arteries (n=12) were isolated and
pressurized in a special arteriograph that allowed control of
intravascular pressure and measurement of lumen diameter. Intact
arteries in the absence (control) or presence of 3.0 µmol/L
cytochalasin B (CB), an inhibitor of actin polymerization,
were subjected to stepwise increases in pressure from 75 to 200
mm Hg. Lumen diameter was continuously recorded, as was the
pressure at which forced dilatation (loss of tone) occurred. After a
period of time at 200 mm Hg, pressure was returned to 75
mm Hg and the extent of tone recovery was evaluated.
Results—Arteries with and without CB developed a similar amount
of tone during equilibration at 75 mm Hg: percent tone=27±3%
for control versus 29±4% for CB arteries (P>0.05).
However, arteries in the presence of CB could not withstand pressure as
well and underwent FD at significantly lower pressures: 168±5
mm Hg for control versus 142±5 mm Hg for CB arteries
(P<0.01). The amount of tone that arteries regained
after FD when pressure was returned to 75 mm Hg was also less in
CB arteries: percent tone=34±3% for control versus 11±2% for CB
arteries (P<0.01).
Conclusions—Cytoskeletal integrity appears important for
maintaining cerebral arterial diameter during changing
intravascular pressure. In addition, the process of actin
polymerization may be a significant contributor to development of
myogenic tone after forced dilatation.
While cerebral artery diameter is well maintained within the
myogenic pressure range, acute increases in blood pressure beyond the
limit of autoregulation result in forced dilatation (FD) of cerebral
vessels, autoregulatory breakthrough, and disruption of the blood-brain
barrier.12 13 14 15 The consequence of these events is
elevated arteriolar pressure and a marked increase in cerebral blood
flow and vascular permeability, all of which contribute to the
development of hypertensive encephalopathy.15 16 17 18 19 20 21 22
The vasodilation associated with FD in response to severe acute
hypertension is usually ascribed to stretching of the vessels by the
increased intravascular pressure, which overcomes the autoregulatory
contraction of the VSM. This autoregulatory breakthrough of cerebral
vessels has been shown in most23 24 but not
all21 studies to be reversible once blood
pressure is returned to normal; however, the mechanism of tone recovery
as well as the process of FD is not known.
We hypothesized that a dynamic actin cytoskeleton contributes to
arterial diameter regulation during changing intravascular
pressure and that FD results in disruption of actin filaments.
Therefore, repolymerization of actin filaments may be necessary for
tone recovery after FD. To test this, cannulated and pressurized
cerebral arteries were subjected to increases in intraluminal pressure
in the absence or presence of cytochalasin B (CB), a specific
inhibitor of actin
polymerization,25 26 to investigate the
contribution of actin polymerization in modulating myogenic reactivity
and FD.
Pressurized Arteriograph and Measurement of Lumen Diameter
Each of two arteriograph chambers contained a set of proximal and
distal glass microcannulas (tip=50 µm) on which an artery was
mounted, secured with single strands of nylon suture (diameter=10
µm), and perfused gently with oxygenated PSS. The
proximal cannula was attached to an in-line pressure transducer and
servomechanism that continually measured and adjusted TMP. The servo
system consisted of a small peristaltic pump and controller that
permitted TMP to either be maintained at a set pressure (static) or
increased at a variable rate. In these experiments, the distal
cannulas were closed off so that there was no flow through the
vessels.
Once both arteries were cannulated and pressurized, the arteriograph
was transferred to the stage of an inverted microscope with an attached
video camera and monochrome monitor. Each cannulated artery was
suspended on bulkheads just above an optical window in the bottom of
the chamber, which allowed for viewing of the artery and electronic
measurement of lumen diameter by a technique previously
published.27 Briefly, the transilluminated image
of the artery on the video monitor was used to electronically determine
the dimensions of the artery by the video dimensional analyzer.
The video signal was input to the video dimension analyzer, in
which the optical contrast of the vessel wall was used to initiate and
terminate a voltage ramp, the amplitude of which was proportionate to
the inner diameter.28 The output (analog
voltages) from the video dimension analyzer and the pressure
controller was connected to a computer by a serial data acquisition
system (DATAQ) to record dynamic responses of diameter and TMP.
Experimental Protocols
Several arteries (n=6) were given 3.0 µmol/L CB at 75
mm Hg after equilibration and approximately 5 minutes before pressure
was increased. This concentration of CB did not alter baseline
diameter. Pressure was then increased stepwise in these arteries, as
described above. Since these arteries did not redevelop significant
tone after FD once pressure was returned to 75 mm Hg, arteries
were given 1.0 µmol/L ILV, a specific activator of
protein kinase C and potent smooth muscle cell
constrictor,29 to test for
contractility and viability.
After each experiment, 0.1 mmol/L papaverine was applied to induce
relaxation and obtain a fully relaxed diameter at each transmural
pressure.
Data Calculations and Statistical Analysis
Drugs and Solutions
Figure 1B
Pressure-Diameter Response: Effect of Cytochalasin B
Extent of Tone Recovery After FD: Effect of Cytochalasin B
Control for the Effect and Specificity of Cytochalasin B
In nonmuscle cells, the actin cytoskeleton is a dynamic structure that
responds to mechanical stimuli such as tension with polymerization of
monomeric globular (G-) actin into filamentous (F-) actin, thereby
increasing the number of actin cables.6 7 8 9 10 It is
possible that, similar to nonmuscle cells, the actin cytoskeleton of
VSM also responds to pressure with polymerization of monomeric actin
stores into filaments, thus contributing to myogenic reactivity. We
therefore hypothesized that arteries in which actin polymerization was
inhibited would have a diminished capacity to regulate diameter. In
addition, FD would result in disruption of the actin cytoskeleton, and
repolymerization of actin filaments would be necessary for recovery of
tone after FD. Since arteries in the presence of CB had decreased
reactivity to pressure (Figures 1
In a related study, we determined that induction of actin
polymerization by jasplakinolide, a cell-permeable inducer of actin
polymerization,30 produced contraction and
increased the level of tone in cerebral arteries by
29%.31 In addition, arteries at a pressure of
125 mm Hg that had diameters similar to those of arteries at
75 mm Hg (136±2 versus 133±11 µm) had considerably less
G-actin content (as determined by fixing the arteries pressurized,
staining for G-actin with DNase I, and viewing the arteries with the
use of confocal microscopy), indicating a G- to F-actin transition in
cerebral artery VSM in response to the higher pressure. Together with
the present study, these results suggest that actin polymerization
is a mechanism by which VSM can increase force production in
response to elevated pressure and maintain
diameter.31 While the mechanism by which actin
polymerization is induced by pressure is not clear, the
mechanotransduction of pressure into a cellular response, such as actin
polymerization, has been shown in other cell types to involve a complex
array of integrin molecules and extracellular
linkages,10 which may exist similarly in smooth
muscle and underlie myogenic responses.
A few studies have also investigated the dynamic nature of the actin
cytoskeleton in smooth muscle. Mauss et al32
showed that inhibition of actin polymerization by Clostridium
botulinum C2 toxin (which ADP-ribosylates monomeric G-actin)
impaired the contraction of smooth muscle isolated from guinea pig
ileum. This effect was shown to be caused by a direct action of the
toxin on the smooth muscle. Because filamentous F-actin is not a
substrate for C2 toxin, these findings provide evidence for a role of
G- to F-actin transition in smooth muscle contraction. In a similar
study, when actin polymerization was blocked by CB,
K+-induced contraction of intestinal smooth
muscle cells was inhibited in a dose-dependent manner, without any
significant effect on voltage-dependent calcium channels, membrane
potential, or myosin light chain phosphorylation,
indicating an influence of actin assembly on smooth muscle
contraction.33 The present study, however,
suggests for the first time that myogenic responses (ie,
pressure-dependent contraction) of cerebral arteries was diminished
when actin polymerization was blocked by CB.
Cytochalasins have been shown to have other cellular effects in
addition that of blocking actin polymerization, including inhibiting
glucose transport and promoting depolymerization of
actin microfilaments.25 26 We do not believe that
inhibition of glucose transport by CB is significant in this study
because we have observed that arteries can maintain tone in the absence
of exogenous glucose in excess of 2 hours (M.J.C., unpublished data,
1995). The possibility that CB may be causing
depolymerization of actin filaments is also
unlikely considering that at this concentration of CB, baseline
arterial diameter was unaltered and arteries maintained
greater than 30% tone. In a related study, we determined that high
concentrations (>50 µmol/L) of cytochalasin D caused dilation
and loss of tone in cerebral arteries.31 These
arteries also had significantly greater G-actin content than arteries
with tone, suggesting that dilation is associated with
depolymerization of actin
filaments.31 These arteries in cytochalasin D not
only lost tone but also could not contract to agonist stimulation,
including ILV. In contrast to the present study, arteries in a low
concentration of CB maintained tone and contracted to ILV, suggesting
that CB was inhibiting polymerization but not causing significant
depolymerization of actin filaments.
The concentration of CB used (3.0 µmol/L) did not alter the
baseline diameter of these arteries, which had diameters and levels of
tone similar to those of control arteries without CB. Figure 2
In conclusion, cerebral artery reactivity to pressure was diminished in
the presence of CB, an inhibitor of actin polymerization.
Arteries also underwent FD at significantly lower pressures, suggesting
that a dynamic actin cytoskeleton is important for myogenic responses.
In addition, arteries regained considerably less tone after FD when
pressure was returned to 75 mm Hg, indicating that the process of
actin polymerization is important for recovery of myogenic tone after
FD.
Received December 3, 1997;
revision received March 12, 1998;
accepted March 19, 1998.
Associate
Editor for Basic Science School of Medicine Medical
College of Virginia Richmond, Virginia
The preceding article by Cipolla and Osol reports evidence that the
forced dilation of cerebral arteries from excessive intravascular
pressure is influenced by treatment with cytochalasin B, an
inhibitor of actin polymerization.
The vessels treated with this enzyme developed more pronounced changes
in reactivity and displayed forced dilation at lower pressures than
controls. This is a clear indication that changes in the cytoskeleton
influence vascular reactivity. Hopefully, this study will generate
additional interest in the complex relationships between cytoskeletal
integrity and function and vascular reactivity.
Received December 3, 1997;
revision received March 12, 1998;
accepted March 19, 1998.
© 1998 American Heart Association, Inc.
Original Contributions
Vascular Smooth Muscle Actin Cytoskeleton in Cerebral Artery Forced Dilatation
Abstract
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
Background and Purpose—We
investigated the role of actin polymerization in regulating
arterial diameter in response to increasing pressure and
modulating forced dilatation of cerebral arteries at pressures above
the upper limit of autoregulation.
Key Words: actin cytoskeleton • cerebral arteries • forced dilatation • rats
Introduction
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
The arteries and
arterioles of the cerebral circulation are highly effective at
maintaining cerebrovascular resistance and autoregulation of blood flow
over a wide range of pressures, primarily as a result of the myogenic
mechanisms of the surrounding VSM.1 2 3 4 Myogenic
reactivity is the process by which VSM increases force
production in response to elevated intravascular pressure to
maintain diameter, thus contributing to autoregulation of cerebral
blood flow.3 4 This process is thought to involve
several mechanisms within VSM, including stretch-activated
calcium channels, membrane potential, and intracellular signaling via
protein kinase C and phospholipase C (for review, see Reference 55 ).
However, in most nonmuscle cells, mechanotransduction of pressure into
a cellular response occurs via the actin
cytoskeleton.6 7 8 9 10 Pressure or stretch is sensed,
and the cell responds with rapid polymerization of globular actin into
filaments and stress fiber formation.8 9 10 Since
VSM is phenotypically most similar to nonmuscle cells such as
fibroblasts,11 in that it does not contain
distinct striations or myofibrils, it is possible that the process of
actin polymerization occurs in VSM in response to pressure and
contributes to diameter regulation of cerebral arteries to elevated
intravascular pressure.
Materials and Methods
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
Preparation of Arterial Segments
Male Wistar rats (n=12; B&K Universal, Fremont, Calif) weighing
270 to 320 g were used for all experiments. The rats were lightly
anesthetized with ether and quickly decapitated, as approved by
the Oregon Health Sciences University Animal Care Facility. After
decapitation, the entire brain was removed and placed in cold (4°C)
and oxygenated PSS. A third-order branch of the posterior
cerebral artery (inner diameter=131±5 µm at 75 mm Hg),
identified from specific anatomic location, was carefully dissected and
cleared of connective tissue. Once excised, the arteries were
transferred directly into the arteriograph chambers.
The arteriograph (Living Systems Instrumentation) consisted of
two 10-mL chambers with inlet and outlet ports to allow for superfusion
of the arteries with PSS and for application of drugs. The
superfusate (PSS) was continually recirculated from a 50-mL
reservoir and pumped with a peristaltic pump through a heat exchanger
to warm the PSS to 37°C before it entered the arteriograph chamber.
The PSS was aerated in the reservoir with a mixture of 10%
O2/5% CO2/85%
N2 to maintain a constant pH of 7.4±0.05.
All arteries (n=12) for experimentation were equilibrated for 1
hour at 75 mm Hg, during which time spontaneous tone developed.
After equilibration, pressure was increased in 25-mm Hg increments to
200 mm Hg. The diameter at each pressure as well as the pressure
at which FD occurred was recorded. After the arteries were at
200 mm Hg for approximately 5 minutes, the pressure was lowered
to 75 mm Hg. Arteries were left at 75 mm Hg for 20 to 30
minutes, and the diameter and the amount of tone recovered was
recorded.
All results are presented as mean±SE. The amount of
intrinsic tone an artery possessed was calculated as a percent decrease
in lumen diameter from the relaxed diameter in 0.1 mmol/L
papaverine. Differences between arteries with and without CB were
determined with ANOVA. Differences before and after FD were determined
with ANOVA with repeated measures and considered significant at
P<0.05.
The perfusate and superfusate for all
experiments consisted of a bicarbonate-based phosphate buffer
(Ringer's PSS), the composition of which was as follows (mmol/L): NaCl
119.0, NaHCO3 24.0, KCl 4.7,
KH2PO4 ·
7H2O 1.17, CaCl2 1.6, EDTA
0.026, and glucose 5.5. PSS was made fresh each week and stored without
glucose at 4°C. Glucose was added to the PSS before each experiment.
CB was purchased from Calbiochem. A stock solution of
10-2 mol/L CB in dimethylsulfoxide
was mixed each week and stored at -20°C. ILV was purchased from LC
Laboratories and mixed as 10-3 and
10-4 mol/L stock solutions each
week. Papaverine was purchased from Sigma Chemical Co and mixed as a
10-2 mol/L stock solution each week and stored
at 4°C.
Results
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
Response of Arteries in the Absence and Presence of
Cytochalasin B
Arteries in the presence of CB underwent FD at significantly lower
pressures and regained considerably less tone than control arteries
without CB. The diameter and pressure tracings shown in Figure 1A
demonstrate the typical response of a
control artery to elevated pressure. This vessel developed intrinsic
tone during equilibration and maintained a constant diameter of
120 µm from 75 to 125 mm Hg. When pressure was increased
to 150 mm Hg, the artery began to dilate to the elevated
distending pressure and underwent FD (lost tone) when pressure was
increased to 175 mm Hg. Additional increases in pressure caused
further dilation and increased diameter, thus demonstrating a lack of
myogenicity at pressures beyond the myogenic range. When pressure was
returned to 75 mm Hg, the artery regained tone to a greater
extent than before the pressure was increased, and diameter was below
baseline at 105 µm.
View larger version (13K):
[in a new window]
Figure 1. A, Diameter and pressure tracings of an intact
artery subjected to stepwise increases in intravascular pressure.
Pressures above 125 mm Hg are shown, with FD occurring at
175 mm Hg. When pressure was returned to 75 mm Hg, the
artery regained tone. B, Diameter and pressure tracings of an artery in
CB (3.0 µmol/L) subjected to stepwise increases in TMP.
Pressures above 100 mm Hg are shown, with FD occurring at
150 mm Hg. Note that little tone was restored when pressure was
returned to 75 mm Hg. 
demonstrates the behavior of arteries when actin
polymerization was inhibited in the presence of CB.
Arterial dilation began at 125 mm Hg, and FD occurred
when pressure was increased to 150 mm Hg. This artery regained
little tone when pressure was returned to 75 mm Hg. The amount of
tone present in each artery type before and after FD, as well as
the pressure at which FD occurred, is shown in the
Table.
View this table:
[in a new window]
Table 1. Pressure of FD and Percent Constriction Before and After
FD
The presence of CB did not affect basal diameter, which was
131±4 µm in control and 125±9 µm in CB arteries
(P>0.05) after equilibration at 75 mm Hg. In
addition, the amount of tone was similar between the groups at 75
mm Hg before pressure was increased: percent tone=27±3% for control
arteries and 29±4% for CB arteries (P>0.05). However,
arteries in the presence of CB could not withstand pressure as well
when it was increased to 200 mm Hg, and they underwent FD at
significantly lower pressures. FD occurred at 168±5 mm Hg for
control versus 142±5 mm Hg for CB arteries (P<0.01),
as shown in the Table. Figure 2 shows the
pressure-diameter response of arteries in the absence and presence of
CB.
View larger version (18K):
[in a new window]
Figure 2. Diameter versus TMP for intact arteries in the
absence and presence of CB (3.0 µmol/L).
**P<0.01.
After FD, when pressure was returned to 75 mm Hg, control
arteries regained a somewhat higher, but not statistically significant,
level of intrinsic tone than before pressure was increased (Table);
however, arteries in the presence of CB regained little tone when
pressure was returned to 75 mm Hg. The amount of tone recovered
at 75 mm Hg after FD was 34±3% for control (P>0.05
versus control before FD) and 11±2% for CB arteries
(P<0.01 versus control after FD and versus CB before
FD).
To determine whether arteries in CB that did not regain tone after
FD were not damaged or rendered incapable of constricting in CB,
arteries were given 1.0 µmol/L ILV after FD. Addition of this
compound constricted arteries in CB by 38±5%. However, when pressure
was then increased in these arteries, they could not withstand pressure
and dilated. The diameter and pressure tracings shown in Figure 3A demonstrate this behavior. This artery
was initially in PSS and developed tone on increasing pressure greater
than 50 mm Hg. FD began at 150 mm Hg, and tone was lost
when pressure was increased to 175 mm Hg. When pressure was
returned to 75 mm Hg, the artery regained all tone, and diameter
was below baseline. After FD and recovery of tone, CB (3.0
µmol/L) was added to the bath, which did not alter baseline diameter.
Pressure was again increased in the presence of CB, and FD began at a
lower pressure (125 mm Hg); tone was lost at 150 mm Hg.
When pressure was returned to 75 mm Hg, little tone was restored.
However, when ILV (1.0 µmol/L) was added to the bath, the artery
constricted well below baseline. When pressure was increased in the
constricted artery to 100 mm Hg, the artery could not withstand
the increased pressure and dilated. A graph of the percent constriction
of intact arteries at 75 mm Hg in the presence of CB before FD,
after FD, after FD constricted in ILV, and after FD in ILV after
pressure was increased to 100 mm Hg is shown in Figure 3B.
View larger version (14K):
[in a new window]
Figure 3. A, Diameter and pressure tracings demonstrating
the effect of CB on cerebral artery myogenic reactivity. This cerebral
artery was initially in PSS, and spontaneous tone developed when
pressure was increased more than 50 mm Hg. FD occurred at
150 mm Hg, after which tone was restored when pressure was
returned to 75 mm Hg. The artery was then given 3.0 µmol/L
CB, which did not alter baseline diameter, but when pressure was
increased again, the artery underwent FD at 125 mm Hg and
regained little tone once pressure was returned to 75 mm Hg.
Although this artery developed little pressure-dependent tone after FD,
addition of ILV (1.0 µmol/L) caused contraction in the presence
of CB. However, when pressure was then increased to 100 mm Hg,
the artery could not maintain diameter and dilated to the elevated
intravascular pressure. B, Percent constriction in the presence of
3.0 µmol/L CB before FD, after FD, after FD contracted in
1.0 µmol/L ILV, and after FD in ILV after pressure was increased
to 100 mm Hg. *P<0.05;
**P<0.01.
Discussion
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
The present study demonstrates that the highly effective
regulation of cerebral artery diameter in response to changes in
intravascular pressure (myogenic reactivity) is altered in the presence
of CB, an inhibitor of actin
polymerization.25 26 This was shown by the
finding that arteries in the presence of CB, which had an amount of
basal tone similar to that of control arteries, underwent FD at
significantly lower pressures than arteries without CB. In addition,
arteries without CB regained myogenic tone after FD when pressure was
returned to 75 mm Hg; however, this behavior did not occur in the
presence of CB, suggesting that actin polymerization may be an
important mediator of myogenic activity and cerebral artery responses
to pressure. and 2) and regained significantly
less tone after FD when pressure was returned to 75 mm Hg
(Table), the process of actin polymerization as a mechanism of
increasing force production in VSM in response to pressure
appears likely. shows
that the diameter of arteries was 131±4 µm for control and
125±9 µm for CB arteries (P>0.05) after
equilibration at 75 mm Hg. This was not a statistically
significant difference and likely not biologically significant either
since the amount of basal myogenic tone was also similar between the
groups (27±3% for control and 29±4% for CB arteries;
P>0.05). This is an important consideration since arteries
that are more or less contracted would have a different wall tension
and therefore may respond differently to pressure. Along these lines,
another group of arteries were denuded of endothelium
(data not shown) and were more contracted than intact arteries, likely
due to the loss of endothelium-derived nitric oxide.
The diameter of these denuded arteries was 104±6 µm at 75
mm Hg, and the basal myogenic tone was 42±3%. It is interesting that
these arteries could much better withstand pressure than intact
arteries and underwent FD at 191±5 mm Hg. This was not the case
for denuded arteries in the presence of CB. These arteries were more
contracted (diameter=93±10 µm; percent tone=53±4%) but
underwent FD at much lower pressures (158±5 mm Hg). Therefore,
it appears that under normal conditions, a more contracted state
protects from overdistension and FD, but when actin polymerization is
inhibited by CB, myogenicity is diminished. While the role of the
endothelium in this response is not apparent, it is
clear that both intact and denuded arteries in the presence of CB had
diminished reactivity to pressure and underwent FD at lower pressures,
further suggesting a role for actin polymerization in mediating
myogenic responses.
Selected Abbreviations and Acronyms
CB
=
cytochalasin B
FD
=
forced dilatation
ILV
=
indolactam V
PSS
=
physiological saline solution
TMP
=
transmural pressure
VSM
=
vascular smooth muscle
Acknowledgments
This study was supported by American Heart Association
Grant-in-Aid 93014090. We would like to acknowledge Kathi Derrickson
and Nicole Bang of the Surgery Graphics Department at Oregon Health
Sciences University for their expert assistance with the
figures.
References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
Editorial Comment
Introduction
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
Pronounced, acute increases in arterial blood pressure
induce severe and extensive changes in the cerebral vasculature. Such
changes are associated with histological changes in the
endothelium and vascular smooth muscle; marked,
sometimes uneven, sustained vasodilation; increased permeability to
macromolecules; and alterations in the reactivity of the
vessels.1 These changes are partly mediated by
generation of oxygen radicals, since they are either prevented or
minimized by pretreatment with scavengers of these
radicals.1 Interest in this phenomenon resides,
in part, in the possibility that it may be a model for human
hypertensive encephalopathy.2
Selected Abbreviations and Acronyms
CB
=
cytochalasin B
FD
=
forced dilatation
ILV
=
indolactam V
PSS
=
physiological saline solution
TMP
=
transmural pressure
VSM
=
vascular smooth muscle
References
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
Introduction
References
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S. C. Fagan, D. C. Hess, E. J. Hohnadel, D. M. Pollock, and A. Ergul Targets for Vascular Protection After Acute Ischemic Stroke Stroke, September 1, 2004; 35(9): 2220 - 2225. [Abstract] [Full Text] [PDF]
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M. J. Cipolla, L. Vitullo, and J. McKinnon Cerebral artery reactivity changes during pregnancy and the postpartum period: a role in eclampsia? Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2127 - H2132. [Abstract] [Full Text] [PDF]
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D. D. Tang and J. Tan Downregulation of profilin with antisense oligodeoxynucleotides inhibits force development during stimulation of smooth muscle Am J Physiol Heart Circ Physiol, October 1, 2003; 285(4): H1528 - H1536. [Abstract] [Full Text] [PDF]
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D. D. Tang and J. Tan Role of Crk-Associated Substrate in the Regulation of Vascular Smooth Muscle Contraction Hypertension, October 1, 2003; 42(4): 858 - 863. [Abstract] [Full Text] [PDF]
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J. Goldman, L. Zhong, and S. Q. Liu Degradation of alpha -actin filaments in venous smooth muscle cells in response to mechanical stretch Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1839 - H1847. [Abstract] [Full Text] [PDF]
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G. Lagaud, N. Gaudreault, E. D. W. Moore, C. van Breemen, and I. Laher Pressure-dependent myogenic constriction of cerebral arteries occurs independently of voltage-dependent activation Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2187 - H2195. [Abstract] [Full Text] [PDF]
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M. Ishiguro, C. B. Puryear, E. Bisson, C. M. Saundry, D. J. Nathan, S. R. Russell, B. I. Tranmer, and G. C. Wellman Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2217 - H2225. [Abstract] [Full Text] [PDF]
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G. Osol, J. F. Brekke, K. McElroy-Yaggy, and N. I. Gokina Myogenic tone, reactivity, and forced dilatation: a three-phase model of in vitro arterial myogenic behavior Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2260 - H2267. [Abstract] [Full Text] [PDF]
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 M. J. CIPOLLA, N. I. GOKINA, and G. OSOL Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior FASEB J, January 1, 2002; 16(1): 72 - 76. [Abstract] [Full Text] [PDF]
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 W. T. Gerthoffer and S. J. Gunst Signal Transduction in Smooth Muscle: Invited Review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle J Appl Physiol, August 1, 2001; 91(2): 963 - 972. [Abstract] [Full Text] [PDF]
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