From the Cardiovascular Division, Department of Medicine, University of
Minnesota (Minneapolis).
Correspondence to Alan J. Bank, MD, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware St SE, Minneapolis, MN 55455. E-mail bankx001{at}maroon.tc.umn.edu
Abstract
Abstract—Compliance, distensibility,
incremental elastic modulus (Einc), and pulse wave velocity
are all terms used to describe the mechanical properties of arteries.
Previous studies assessing the effects of smooth muscle relaxation on
each of these parameters have produced conflicting results.
Our laboratory has previously demonstrated that intrabrachial infusion
of nitroglycerin in normal human subjects results in a
large increase in brachial artery compliance without changing
arterial wall stiffness as measured by Einc. In
the present study, the relationships among compliance,
distensibility, Einc, and pulse wave velocity under
different levels of vascular tone are shown using data acquired by
intravascular ultrasound as well as theoretical curves. We demonstrate
that the effects of smooth muscle relaxation can be depicted as 2
separate steps: (1) a rightward shift to a new theoretical curve
describing the relationship between 2 of the above elastic
parameters that is solely due to changes in vessel geometry
and (2) a shift along the new curve that is dependent on changes in
wall stiffness.
Anumber of different
terms are used to describe the mechanical properties of arteries. These
include compliance, distensibility, incremental elastic modulus
(Einc), and pulse wave velocity (PWV), among
others. The effects of smooth muscle relaxation on these
parameters are complicated and controversial. For example,
smooth muscle relaxation has been reported to decrease
Einc,1 increase
Einc,2 3 increase
distensibility,4 5 and increase
compliance.6 7 There are a number of potential
explanations for these conflicting results, including isobaric versus
isometric analysis of data, different techniques and research
conditions, and direct versus indirect (systemic) effects of drugs in
the various studies. One additional possible source of difficulty in
interpreting the effects of smooth muscle relaxation on
arterial mechanical properties relates to the terms used.
It is often assumed that a directional change in 1 of these measures of
arterial elasticity after an intervention (such as drug
therapy) necessarily implies an automatic and predetermined directional
change of another. For example, an increase in compliance of an artery
after administration of a smooth muscle vasodilator is assumed to
result in a decrease in arterial Einc
because these terms are inversely related.
We have previously reported that in vivo human brachial artery smooth
muscle relaxation with nitroglycerin results in a large
(
Methods
Study Population
Intravascular Ultrasound
Arterial Elastic Parameters
Theoretical Curves
Intra-arterial nitroglycerin resulted in an
Statistics
Results
Measured compliance and Einc at 95
mm Hg were 0.010±0.001 mm2/mm Hg and
38±6x106 dyne/cm2 for
baseline and 0.015±0.001 mm2/mm Hg and
37±6x106 dyne/cm2 for
nitroglycerin conditions. These points are plotted in
Figure 1
Measured distensibility at 95 mm Hg did not significantly change
with nitroglycerin (5.05±0.86 versus 5.80±0.55
10-4/mm Hg) but PWV significantly decreased
(P<0.05) from 15.1±1.1 to 13.2±0.7 m/s at 95 mm Hg.
Figure 2
Discussion
The present study demonstrates that brachial artery
vasodilation with nitroglycerin in normal human
subjects results in a significant increase in compliance and decrease
in PWV without producing any significant changes in
arterial Einc or distensibility. By
use of measured data and theoretical curves, the relationships among
these 4 variables are depicted. These curves emphasize that smooth
muscle relaxation results in changes in vessel stiffness and geometry.
The net effect of smooth muscle relaxation depends on the balance of
these stiffness and geometric effects. Measuring a change in a given
mechanical parameter after smooth muscle relaxation does
not necessarily allow one to infer the direction or magnitude of a
change in a different parameter.
The terms compliance, PWV, Einc, and
distensibility are all used to describe mechanical properties of
arteries. At a given vessel geometry (radius and wall thickness), it is
clear that compliance, for example, is directly related to
distensibility and indirectly related to Einc and
PWV. However, once vessel geometry is changed by vasodilation, the
relationships among these variables change. Because the
arterial wall is essentially
incompressible,12 13 wall cross-sectional area is
a constant, and thus wall thickness can be calculated for any change in
vessel radius. Figure 1
The magnitude of the rightward shift of the new
compliance-Einc curve is directly related to the
magnitude of the vasodilation. The shift along the new
compliance-Einc curve is a result of a number of
different factors that occur as a result of smooth muscle relaxation
and that have an impact on arterial stiffness. Smooth
muscle relaxation decreases arterial stiffness by reducing
tension generated by the smooth muscle itself. In addition, tension
generated by the connective tissue elements in series with the smooth
muscle is reduced. On the other hand, smooth muscle relaxation
increases arterial stiffness by "engaging" stiff
collagen fibers that have previously been slack14
and by tensing elastin fibers, both of which are in parallel with the
smooth muscle in the arterial wall.
Figure 4
In this last situation, the vessel has become more compliant yet
stiffer. Although this at first appears to be a mistake, it is not. The
geometric advantage gained by the vessel during vasodilation
"outweighs" the increase in stiffness that occurs, and the net
result is an increase in compliance. Compliance, like PWV, is a term
that is dependent on both vessel geometry and stiffness. In contrast,
distensibility and Einc are terms that describe
the stiffness of the vessel wall and are independent of geometry. If
one measures a parameter that incorporates geometry and
stiffness (compliance or PWV) before and after vasodilation, then the
effect of vasodilation on the other parameter can be
predicted. If one measures a stiffness parameter
(Einc or distensibility) before and after
vasodilation, then the effect of vasodilation on the other stiffness
parameter can be predicted. This is shown in Figures 2
Measured data and theoretical curves shown in this study depict
relationships among the variables at 95 mm Hg transmural
pressure only. However, curves can be generated for isobaric smooth
muscle relaxation at any pressure, and they will show similar effects.
Curves can also be generated to depict the relationships among the
variables that follow smooth muscle contraction. Smooth muscle
contraction will simply result in a leftward shift of the curves shown
that is proportional to the magnitude of the vasoconstriction. Shifts
along the new curve will be dependent on alterations in vascular
stiffness.
In summary, we demonstrate that intra-arterial
nitroglycerin directly increases brachial artery
compliance and decreases PWV without altering arterial
Einc or distensibility in normal human subjects.
Compliance increases and PWV decreases due to vasodilation and
geometric effects, not as a result of changes in arterial
wall stiffness. The separate effects on geometry and stiffness can be
visualized by plotting theoretical curves that describe the
relationships among the variables in compliance, distensibility,
Einc, and PWV under different conditions of
smooth muscle tone. An increase in arterial compliance or a
decrease in PWV with smooth muscle relaxation can potentially occur in
concert with an increase, a decrease, or no change in vessel wall
stiffness.
Acknowledgments
This study was supported in part by an American Heart
Association Grant-in-Aid, a University of Minnesota Faculty
grant-in-aid, National Institutes of Health Program project grant
PO1-HL-32427, and General Clinical Research Center grant
M01-RR-00400.
Received January 24, 1998;
first decision February 5, 1998;
accepted April 7, 1998.
References
1.
Peterson LH, Jensen RE, Parnell J. Mechanical
properties of arteries in vivo. Circ Res. 1960;8:622–639.
2.
Dobrin PB, Rovick AA. Influence of vascular smooth
muscle on contractile mechanics and elasticity of arteries.
Am J Physiol. 1969;217:1644–1652.
3.
Barra JG, Armentano RL, Levenson J, Fischer EIC,
Pichel RH, Simon A. Assessment of smooth muscle contribution to
descending thoracic aortic elastic mechanics in conscious dogs.
Circ Res. 1993;73:1040–1050.
4.
Yano M, Kumada T, Matsuzaki M, Kohno M, Hiro T,
Kohtoku S, Miura T, Katayama K, Ozaki M, Kusukawa R. Effect of
diltiazem on aortic pressure-diameter relationship in dogs.
Am J Physiol. 1989;256:H1580–H1587.
5.
Stefanadis C, Dernellis J, Vlachopoulos C, Tsioufis C,
Tsiamis E, Toutouzas K, Pitsavos C, Toutouzas P. Aortic function in
arterial hypertension determined by pressure-diameter
relation: effects of diltiazem. Circulation. 1997;96:1853–1858.
6.
Safar ME, London GM, Bouthier JA, Levenson JA, Laurent
S. Brachial artery cross-sectional area and distensibility before and
after arteriolar vasodilation in men with sustained hypertension.
J Cardiovasc Pharmacol. 1987;9:734–742.[Medline]
[Order article via Infotrieve]
7.
Fitchett DH. Forearm arterial compliance:
a new measure of arterial compliance. Cardiovasc
Res. 1984;18:651–656.[Medline]
[Order article via Infotrieve]
8.
Bank AJ, Wilson RF, Kubo SH, Holte JE, Dresing TJ,
Wang H. Direct effects of smooth muscle relaxation and contraction on
in vivo human brachial artery elastic properties. Circ Res. 1995;77:1008–1016.
9.
Bank AJ, Wang H, Holte J, Mullen K, Shammas R, Kubo
SH. Contribution of collagen, elastin, and smooth muscle to in vivo
human brachial artery wall stress and elastic modulus.
Circulation. 1996;94:3263–3270.
10.
Milnor WR. Properties of the vascular wall. In: Milnor
WR, ed. Hemodynamics. Baltimore, Md:
Williams & Wilkins Co; 1982:56–96.
11.
Langewouters GJ, Wesseling KH, Goedhard WJA. The static
elastic properties of 45 human thoracic and 20 abdominal aortas in
vitro and the parameters of a new model. J
Biomech. 1984;17:425–435.[Medline]
[Order article via Infotrieve]
12.
Lawton RW. The thermoelastic behavior of isolated
aortic strips in the dog. Circ Res. 1954;2:344–353.
13.
Carew TE, Vaishnau RN, Patel DJ. Compressibility
of the arterial wall. Circ Res. 1968;23:61–68.
14.
Roach MR, Burton AC. The reason for the shape of the
distensibility curves of arteries. Can J Biochem
Physiol. 1957;35:681–690.
© 1998 American Heart Association, Inc.
Third Workshop on Structure and Function of Large
Arteries: Part II
Smooth Muscle Relaxation
Effects on Arterial Compliance, Distensibility, Elastic Modulus, and Pulse Wave Velocity
Key Words: arteries • compliance • elasticity • vasodilation • muscle, smooth
50%) increase in arterial compliance without any
significant change in
Einc.8 In the present
study, we determined brachial artery compliance,
Einc, distensibility, and PWV in normal human
subjects in vivo using a recently described intravascular ultrasound
technique.8 9 We then generated theoretical
curves to describe the relationships among these 4 variables at
baseline and after smooth muscle relaxation with
intra-arterial nitroglycerin. We
demonstrate that smooth muscle relaxation can be viewed as 2 separate
effects. The first is a rightward shift to a new theoretical curve
describing the relationship between the 2 variables that is
proportional to the magnitude of the vasodilation and is solely a
geometric effect. The second is a shift along the new curve that is
dependent only on the change in vessel stiffness.
Brachial artery elastic mechanics were measured in 8 normal
human subjects of mean±SD age 37.5±4.4 years (range, 22 to 51 years).
These subjects were without significant medical problems as assessed by
history, physical examination, ECG, and routine blood tests. Written
informed consent was obtained from all subjects. This study was
approved by the Institutional Research Board at the University of
Minnesota.
The details of this technique, including reproducibility of the
measurements, have been previously described.8
The brachial artery was imaged using a commercially available
intravascular ultrasound (IVUS) system (HP Sonos Intravascular Imaging
System, Hewlett Packard Co). Briefly, a 3.5F or 4.0F monorail IVUS
catheter with a 30-MHz mechanical rotating transducer (Boston
Scientific Corp) was placed through a sheath into the brachial artery.
Simultaneous brachial artery pressure and IVUS images were
obtained so that arterial pressure, cross-sectional area,
and wall thickness could be determined off-line at any point in the
cardiac cycle. Transmural pressure was reduced by inflating a
pressurized upper arm cuff overlying the IVUS catheter and was defined
as intra-arterial minus cuff pressure. Bolus infusions of
nitroglycerin (100 µg) were administered through a
sidearm of the arterial sheath at doses that altered
brachial artery smooth muscle tone without producing changes in blood
pressure or other systemic effects. This technique allowed the study of
brachial artery elastic properties over a wide range of transmural
pressure and smooth muscle tone. Brachial artery images were captured
and analyzed using a Macintosh IIci personal computer,
framegrabber (Data Translations-QuickCapture), and the NIH Image
program.
Compliance at any given pressure was calculated as the tangent
or first derivative of the pressure-luminal area curve (dA/dP).
Distensibility was defined as the compliance at a given pressure
divided by a reference area. Wall stress was calculated using
Laplace's Law as transmural pressure multiplied by midwall radius
divided by wall thickness (h). Strain was calculated as radius at a
given pressure divided by effective unstressed radius (vessel radius at
0 mm Hg transmural pressure). Einc was
defined as 0.75 multiplied by the tangent or first derivative of the
stress-strain curve.2 PWV was calculated
according to the Moens-Koertewig equation10:
PWV=[(Eincxh)/(2
xri)]1/2,
where is blood density and ri is vessel inner
radius. Pressure-area and stress-strain data were fit to an arctangent
equation,11 with all individual curves resulting
in r values of 0.96 or greater.
Brachial artery compliance, distensibility,
Einc, and PWV were measured or calculated over a
wide pressure range (between 0 and 100 mm Hg transmural
pressure). In the present study, only the data acquired at a mean
transmural pressure of 95 mm Hg were used. Theoretical curves
describing the relationship between compliance and
Einc under different levels of smooth muscle tone
were generated as follows. The mean pressure-area relationship of the
brachial artery in the 8 normal subjects was assumed to be linear
between 90 and 100 mm Hg, and wall cross-sectional area was
assumed to be constant.12 13 Actual compliance
and Einc were first measured at transmural
pressures of 90 and 100 mm Hg under baseline conditions. The
theoretical relationship between compliance and
Einc at a mean pressure of 95 mm Hg was
then calculated for any value of inner radius at 100 mm Hg (ie,
any hypothetical change in vessel size in response to this 10-mm Hg
pressure increment). By substituting a wide range of values of inner
radius at 100 mm Hg for the actual measured values and
calculating the new compliance and Einc for each
value, we determined the theoretical baseline
compliance-Einc relationship for this vessel at a
mean pressure of 95 mm Hg. Theoretical curves demonstrating the
relationships among the other variables under baseline conditions
were made using the same approach. 10% increase in brachial artery radius. The above process was used
to generate the theoretical curves describing the relationships among
the variables under this new condition. Finally, curves were
generated assuming a 20% increase in brachial artery radius after
vasodilator administration.
Effects of nitroglycerin on arterial
elastic parameters were analyzed using paired
t tests. Statistical significance was accepted at
P<0.05. Data are presented as mean±SEM. 
. Nitroglycerin
resulted in a significant increase in brachial artery radius of 10%
(P<0.001) and compliance of 50% (P<0.05)
without change in Einc. The relationship between
compliance and Einc at 95 mm Hg is shown by
the theoretical curves that run through the measured data points under
baseline and 10% dilation conditions. An additional theoretical curve
is also shown assuming 20% increase in radius after vasodilator
administration. As one would expect, under conditions of constant
smooth muscle tone, there is an inverse relationship between
Einc and compliance that is curvilinear and has
the x and y axes as asymptotes. Smooth
muscle relaxation produces an upward and rightward shift of the
Einc-compliance curve, with the magnitude of the
shift directly proportional to the magnitude of the vasodilation. The
vasodilated vessel is more compliant than the vasoconstricted vessel at
the same Einc. The vasodilated vessel also has a
higher Einc at the same compliance.
View larger version (14K):
[in a new window]
Figure 1. Compliance vs incremental elastic modulus
(Einc) curves at 95 mm Hg transmural
arterial pressure under baseline, 10% vasodilation, and
20% vasodilation conditions. Measured data are depicted by
the symbols on the curves. Each curve represents all
theoretical values of compliance and Einc under the
geometric conditions (radius and wall thickness) measured. Vasodilation
shifts the theoretical curves rightward in a dose-dependent
manner. shows curves of compliance
versus 1/distensibility and compliance versus PWV under baseline, 10%
dilation, and 20% dilation conditions. As in the
Einc-compliance curves, the measured data points
are marked on the theoretical curves. Figure 3 shows measured data points and
theoretical curves for other combinations of the 4
parameters assessed in this study. Of note,
Einc-distensibility curves and compliance-PWV
curves under each of the 3 levels of smooth muscle tone are almost
superimposable. In contrast, all other curves show a dose-dependent
rightward shift with smooth muscle relaxation.
View larger version (12K):
[in a new window]
Figure 2. Theoretical curves of compliance versus
1/distensibility and compliance vs pulse wave velocity (PWV) at 95
mm Hg transmural pressure under different levels of vascular tone.
Vasodilation results in a rightward shift of the
compliance-1/distensibility curves but not of the compliance-PWV
curves.
View larger version (12K):
[in a new window]
Figure 3. Theoretical curves depicting the relationships
among incremental elastic modulus (Einc), pulse wave
velocity (PWV), and distensibility at 95 mm Hg transmural
pressure under different levels of vascular tone. Vasodilation produces
a rightward shift of the curves in the first 2 graphs but not in the
third. 
shows the relationship between compliance and
Einc at a mean pressure of 95 mm Hg under 3
conditions: baseline, 10% vasodilation, and 20% vasodilation. Ratios
of radius to wall thickness under the 3 conditions are 10.0, 12.0, and
15.1, respectively. Smooth muscle relaxation results in 2 separate
effects. The first is a rightward shift to a new compliance versus
Einc curve. This new curve describes the
relationship between compliance and Einc under
the new ratio of radius to wall thickness and is due solely to a change
in vessel geometry. The second effect is a shift along the new
compliance versus Einc curve. This shift is
solely a result of the effect of the vasodilator drug on
arterial stiffness and is independent of geometry. shows a close-up of the
compliance-Einc curves at baseline and after a
20% increase in brachial artery radius. Following smooth muscle
relaxation, a number of different possible effects can occur. A shift
to any point in quadrant 1 (point A) results in an increase in
Einc and a decrease in compliance. A shift to any
point in quadrant 3 (point C) results in a decrease in
Einc and an increase in compliance. However, a
shift to any point in quadrant 2 (point B) results in an increase in
both Einc and compliance.
View larger version (16K):
[in a new window]
Figure 4. Theoretical compliance vs incremental elastic
modulus (Einc) curves at a transmural pressure of 95
mm Hg under baseline and 20% dilation conditions. Vasodilation
results in a shift to a new compliance-Einc curve.
Dependent on the change in wall stiffness, vasodilation can result in a
decrease in compliance and an increase in Einc (point A),
an increase in compliance and a decrease in Einc (point C),
or an increase in both compliance and Einc (point B). and 3, where compliance-PWV and Einc-distensibility
curves are nearly superimposable regardless of the magnitude of the
vasodilation. In contrast, one cannot predict the directional effect of
vasodilation on Einc or distensibility by
measuring compliance or PWV.
This article has been cited by other articles:
 |
|
 |
|
  A. R. Malik, V. Kondragunta, and I. J. Kullo Forearm Vascular Reactivity and Arterial Stiffness in Asymptomatic Adults From the Community Hypertension, June 1, 2008; 51(6): 1512 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Rebuttal from Drs. Mcloughlin and Mcmurtry J Appl Physiol, October 1, 2007; 103(4): 1453 - 1454. [Full Text] [PDF]
|
|
|
|
 |
|
 A L Pauca, N D Kon, and M F O'Rourke Benefit of glyceryl trinitrate on arterial stiffness is directly due to effects on peripheral arteries Heart, November 1, 2005; 91(11): 1428 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Santana, J. G. Barra, J. C. Grignola, F. F. Gines, and R. L. Armentano Pulmonary artery smooth muscle activation attenuates arterial dysfunction during acute pulmonary hypertension J Appl Physiol, February 1, 2005; 98(2): 605 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Arroyo-Espliguero, N. Mollichelli, P. Avanzas, E. Zouridakis, V. R Newey, D. K Nassiri, and J. C. Kaski Chronic inflammation and increased arterial stiffness in patients with cardiac syndrome X Eur. Heart J., November 2, 2003; 24(22): 2006 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J.L. Vuurmans, P. Boer, and H. A. Koomans Effects of Endothelin-1 and Endothelin-1 Receptor Blockade on Cardiac Output, Aortic Pressure, and Pulse Wave Velocity in Humans Hypertension, June 1, 2003; 41(6): 1253 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X J Jiang, M F O'Rourke, W Q L Jin, L S Liu, C W Li, P C Tai, X C Zhang, and S Z Liu Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform Heart, August 1, 2002; 88(2): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wronski, E. Seeliger, P. B. Persson, A. Harnath, and B. Flemming Influence of baroreflex on volume elasticity of heart and aorta in the rabbit Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R842 - R849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Kaiser, K. Mullen, and A. J. Bank Brachial Artery Elastic Mechanics in Patients With Heart Failure Hypertension, December 1, 2001; 38(6): 1440 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Yasmin and M.J. Brown Similarities and differences between augmentation index and pulse wave velocity in the assessment of arterial stiffness QJM, October 1, 1999; 92(10): 595 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Bank, D. R. Kaiser, S. Rajala, and A. Cheng In Vivo Human Brachial Artery Elastic Mechanics : Effects of Smooth Muscle Relaxation Circulation, July 6, 1999; 100(1): 41 - 47. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||