Am J Physiol Heart Circ Physiol 290: H1534 –H1539, 2006.
First published October 21 2005; doi:10.1152/ajpheart.00742.2005.
Respective contribution of age, mean arterial pressure, and body weight
on central arterial distensibility in SHR
Carlos Labat,1,5 Roberto S. A. Cunha,3 Pascal Challande,4,6 Michel E. Safar,2,7 and Patrick Lacolley1,5
1
INSERM U684, Nancy, France; 2Hôtel-Dieu Hospital, Diagnosis center, Paris, France; 3UFES,
Clinica de Investigaçao cardiovascular, Vitoria, Brazil; 4CNRS, FRE 2867, Paris, France;
5
Université Henri Poincaré, UFR Médecine, Nancy, France; 6Université Pierre et Marie
Curie, UFR923, Paris, France; and 7Université René Descartes, UFR Médecine, Paris, France
Submitted 14 July 2005; accepted in final form 12 October 2005
rats (SHR), carotid arterial
distensibility measured at the operational steady-state mean
arterial pressure (MAP) of corresponding animals is constantly
reduced compared with that shown in normotensive Wistar or
Wistar-Kyoto controls (9, 12, 19, 20). However, when carotid
distensibility is measured in SHR for the same MAP as in
controls, i.e., in isobaric conditions, the results may differ
substantially according to the animal age. In older SHR,
isobaric carotid distensibility is significantly reduced, suggesting that increased stiffness of wall material, but not MAP level,
is responsible for the reduced arterial elasticity (12). In
younger SHR, isobaric carotid distensibility remains within the
normal range, indicating that a MAP-induced reduction of
elasticity is mainly responsible for the observed results (9). In
SHR, however, there are numerous other situations where
isobaric distensibility was found to be reduced, depending on
the site of arterial measurements, the level of sodium intake, or
the presence of associated neurohumoral factors, such as those
observed under conditions of diabetes mellitus, obesity, and/or
insulin resistance (19). These latter findings are quite important
to consider because these situations influence the local distensibility of central arteries through three main possible modifications: arterial wall structure, smooth muscle tone, and MAP
level. Nevertheless, it is worth noting that only the operational
MAP level is able, at any given time, whether in acute,
short-term or long-term situations, to adapt and optimize the
Windkessel aortic function (20).
The SHR, which is constantly devoid of atherosclerosis and
diabetes mellitus, is an excellent model because it allows us to
evaluate aortic distensibility in hypertensive rats. However,
three methodological difficulties should be considered. First, it
is important to take into account the role of body weight,
which, in recent years, has been shown to be significantly
associated with increased arterial stiffness independently of
MAP and other confounding factors (9, 12, 19, 24). In rat
hypertension, the influence of body weight on distensibility has
not been extensively investigated. Second, in the past, the “in
vitro” static investigations of arterial distensibility have tended
to underestimate not only the role of nonhemodynamic factors
(mainly of endothelial origin) but also the specific impact of
pulse pressure in the mechanism(s) of reduced elasticity. Indeed, whereas, in each individual animal or human model, the
MAP level is quite similar in all parts of the arterial tree,
pulsatile pressure differs markedly according to the site of
blood pressure (BP) measurements, such that pulsatile pressure
is constantly higher in peripheral than in central arteries and
thus requires local specific measurements (13). Finally, the
wide use of pulsatile BP determination may also somewhat
complicate the interpretation of isobaric distensibility in small
rodents. Because of the shift of the distensibility-BP curves in
hypertensive animals compared with normotensive controls,
the level of isobaric BP determinations is frequently based on
the comparison between the diastolic component of the normotensive curve and the systolic component of the hypertensive curve (1, 9, 22, 26). Together, all of these observations
suggest that new procedures are needed to evaluate the “in
vivo” distensibility of normotensive and hypertensive animals
for the same MAP. In humans, many epidemiological and
therapeutic studies have recently shown that the use of multiple
regression analysis and subsequently of various adjustments
between the studied parameters may provide adequate statistical solutions to these important problems (15).
Address for reprint requests and other correspondence: M. E. Safar, Diagnosis Center, Hôtel-Dieu Hospital, 1 place du Parvis Notre-Dame, 75181 Paris
Cedex 04, France (e-mail: [email protected]).
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
spontaneously hypertensive rats; carotid distensibility
IN SPONTANEOUSLY HYPERTENSIVE
H1534
0363-6135/06 $8.00 Copyright © 2006 the American Physiological Society
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Labat, Carlos, Roberto S. A. Cunha, Pascal Challande, Michel E.
Safar, and Patrick Lacolley. Respective contribution of age, mean
arterial pressure, and body weight on central arterial distensibility in
SHR. Am J Physiol Heart Circ Physiol 290: H1534 –H1539, 2006. First
published October 21 2005; doi:10.1152/ajpheart.00742.2005.—In spontaneously hypertensive rats (SHR), carotid and aortic distensibilities
measured at operational blood pressure (BP) are reduced. Increased
body weight and mean arterial pressure (MAP) are both known to
reduce distensibility independently. However, whether, after adjustment to body weight and mean BP, distensibility remains reduced in
SHR has never been investigated. Carotid and abdominal aorta distensibilities were measured under anesthesia in SHR at 5, 12, 52, and
78 wk of age, and measurements were compared with age-matched
normotensive Wistar rats. Each age group was composed of 9 or 10
animals. We determined distensibility using echo-tracking techniques
of high resolution. Compared with Wistar rats, carotid and aortic
distensibilities measured at operational MAP are reduced in SHR.
This reduction is accentuated with age, particularly for the carotid
artery. After adjustment to body weight and MAP, carotid and aortic
distensibilities become identical in Wistar and SHR (or even slightly
increased in SHR) but continue to be reduced with age, mainly for the
carotid artery. In conclusion, in SHR, age and high BP do not have a
parallel and similar influence on the reduction of arterial distensibility.
Aging constantly reduces arterial distensibility, whereas MAP levels
contribute to maintenance of arterial function.
H1535
ADJUSTED DISTENSIBILITY IN SHR
Fig. 1. Mean values of body weight (⫾SE) according to age and strain. Note
that, with age, body weights of spontaneously hypertensive rats (SHR; E)
became smaller than those for Wistar rats (■). There were an age effect (P ⬍
0.0001), strain effect (P ⬍ 0.0001), and significant interaction (P ⬍ 0.0001).
The purpose of the present study was to determine the
changes in the mechanical properties of the carotid artery and
of the abdominal aorta according to age and to evaluate
whether arterial distensibilities differ in normotensive (Wistar
rats) and hypertensive (SHR) animals before and after adjustment to MAP and body weight. In this study, we found that the
operational MAP level of hypertensive animals is one of the
main factors in short- and long-term situations contributing to
windkessel arterial function adaptation, hence continuously
optimizing cardiac-aortic coupling.
冉 冊册
冋
␲
P⫺␤
⫹ tan⫺1
2
␥
Dist共P兲 ⫽
1
␦LCSA
⫻
LCSA
␦P
LCSA ⫽ ␣
Statistical evaluation. Values are presented as means ⫾ SE. For
hemodynamic measurements, a two-way ANOVA was performed,
distinguishing between an age effect, a strain effect, and their interaction. The statistical evaluation was performed independently for
each arterial territory: the initial portion of CCA, used as a close
marker of the proximal thoracic aorta, and the distal abdominal aorta.
For each arterial site, results are presented at different ages before and
after adjustment to body weight and MAP after we had verified that
each factor contributed independently to the regression analysis. A P
value ⬍0.05 was considered significant.
MATERIALS AND METHODS
Animals. All procedures were carried out in accordance with
institutional guidelines for animal experimentation. Male SHR and
Wistar rats were obtained from Iffa-Credo (Lyon, France) at 5, 12, 52,
and 78 wk of age. Each group was composed of 9 or 10 animals. Body
weights are presented in Fig. 1. Above 12 wk of age, body weight was
significantly higher in Wistar rats than in SHR. Animals were housed
in the same environment (25°C, 12:12-h light-dark cycle) and allowed
free access to food and water. The protocol was approved by our
institutional ethical committee of “Institut National de la Santé et de
la Recherche Médicale,” Paris, France.
Hemodynamic investigations. Rats were anesthetized with 50
mg/kg ip phenobarbital. For the carotid proximal thoracic aorta
measurements, a Teflon catheter coupled to a Statham P2SID pressure
transducer was introduced at the initial portion of the right common
RESULTS
CCA measurements. Nonadjusted results for the CCA are
presented in Table 1. BP (systolic and diastolic BP, MAP,
pulsatile pressure) was significantly higher in SHR than in
Table 1. CCA: nonadjusted values of hemodynamic parameters according to age and strain
Age, wk
SBP, mmHg
DBP, mmHg
MAP, mmHg
PP, mmHg
HR, beats/min
Mean diameter, ␮m
Pulsatile diameter, %
Distensibility, mmHg⫺1 ⫻ 10⫺3
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
5
12
52
78
P1
P2
P3
113.2⫾21.4
156.5⫾22.1
84.9⫾3.7
118.4⫾3.8
98.1⫾4.0
136.2⫾4.1
31.4⫾1.8
37.9⫾1.9
436.9⫾14.3
381.1⫾17.8
0.64⫾0.03
0.85⫾0.03
13.5⫾0.6
12.0⫾0.6
9.06⫾0.38
7.48⫾0.41
141.3⫾19.2
190.6⫾23.8
114.1⫾3.3
151.2⫾4.1
128.1⫾3.6
170.3⫾4.4
27.1⫾1.6
39.8⫾2.0
388.4⫾12.8
348.6⫾15.9
0.95⫾0.02
1.05⫾0.03
8.6⫾0.5
7.1⫾0.6
6.75⫾0.35
5.04⫾0.44
207.5⫾18.7
217.6⫾25.9
124.7⫾3.2
161.8⫾4.5
142.2⫾3.5
187.2⫾4.8
35.1⫾1.6
56.1⫾2.2
370.5⫾12.5
312.8⫾17.2
1.26⫾0.02
1.31⫾0.03
5.1⫾0.5
4.1⫾0.7
3.00⫾0.35
1.69⫾0.48
151.9⫾22.9
224.6⫾32.4
119.3⫾4.0
162.5⫾5.6
135.7⫾4.3
183.2⫾6.0
32.8⫾2.0
62.1⫾2.8
⬍0.0001
⬍0.0001
0.69 (NS)
⬍0.0001
⬍0.0001
0.98 (NS)
⬍0.0001
⬍0.0001
0.75 (NS)
⬍0.0001
⬍0.0001
0.0003
1.11⫾0.03
1.43⫾0.04
5.1⫾0.6
5.1⫾0.9
3.36⫾0.42
1.37⫾0.60
⬍0.0001
0.01
0.9 (NS)
⬍0.0001
0.0001
0.0015
⬍0.0001
0.03
0.68 (NS)
⬍0.0001
⬍0.0001
0.90 (NS)
Values are means ⫾ SE. CCA, common carotid artery; SPB, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulsatile
pressure; HR, heart rate; NS, not significant. P1, P value for age effect; P2, P value for strain comparison; P3, P value for interaction.
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carotid artery (CCA). We measured pulsatile diameter simultaneously
on the left CCA using transcutaneous determinations. For the distal
abdominal aorta, a similar catheter was introduced via the abdominal
aorta through the femoral artery. As previously described (1), the
procedure for the abdominal aorta requires an abdominal incision.
CCA and abdominal aorta hemodynamic measurements were performed on different groups of rats successively at weeks 5, 12, 52, and
78. Because an abdominal incision was required for the distal portion
of the aorta, but not the for CCA measurements, steady-state MAP
was not the same in the two sets of experiments. Thus results of the
carotid artery and abdominal aorta are presented separately.
The technique of arterial diameter measurements using an echotracking device (NIUS-01; Asulab, Neuchâtel, Switzerland) has been
previously described (1, 22, 26). The relationship between the pressure and the lumen cross-sectional area (LCSA) was fitted with the
model of Langewouters using an arctangent function and three optimal parameters (␣, ␤, and ␥) (8). Local arterial cross-sectional
compliance, in the case of a cylindrical vessel, was defined by the
change in LCSA for a given change in intravascular pressure (␦P).
Local arterial cross-sectional distensibility (Dist) was calculated as the
relative change in LCSA for a ␦P:
H1536
ADJUSTED DISTENSIBILITY IN SHR
Fig. 2. Common carotid artery (CCA) study: mean values of pulsatile pressure
(PP)-to-mean arterial pressure (MAP) ratio according to age and strain. Note
that, with age, the ratio become higher in SHR (E) than in Wistar rats (■).
There were an age effect (P ⬍ 0.0001), strain effect (P ⫽ 0.0001), and
significant interaction (P ⬍ 0.0001). For simplicity, SE are not indicated.
Fig. 3. CCA study: mean values of pulsatile arterial diameter (%; A) and
distensibility (mmHg-1 ⫻ 10⫺3; B) adjusted for body weight and MAP,
according to age and strain in SHR (E) and Wistar rats (■). See the degree of
significance within each panel. NS, not significant. For simplicity, SE are not
indicated.
Abdominal aorta measurements. Nonadjusted results of the
abdominal aorta are presented in Table 3. They do not differ
markedly from those observed with CCA, except for interactions between age and BP. However, note that, for these
measurements, an abdominal incision was required.
After adjustment to body weight or to MAP or to body
weight and MAP, similar results as for the CCA were also
observed. In particular, for pulsatile diameter and distensibility, no age effect, no strain effect, and no (or a slight) interac-
Table 2. Carotid artery: distensibility according to age and strain and before and after
different adjustments to body weight and MAP
Age, wk
5
12
52
78
P1
P2
P3
3.00⫾0.35
1.69⫾0.48
3.36⫾0.42
1.37⫾0.60
⬍0.0001
⬍0.0001
0.90 (NS)
2.98⫾1.32
1.30⫾0.64
⬍0.0001
⬍0.0001
0.89 (NS)
2.97⫾0.35
3.80⫾0.58
⬍0.0001
⬍0.03
0.78 (NS)
1.73⫾1.07
3.62⫾0.60
⬍0.0001
⬍0.05
0.46 (NS)
Nonadjusted
Distensibility, mmHg⫺1 ⫻ 10⫺3
Wistar
SHR
9.06⫾0.38
7.48⫾0.41
6.75⫾0.35
5.04⫾0.44
Distensibility, mmHg⫺1 ⫻ 10⫺3
Wistar
SHR
9.44⫾1.31
7.87⫾1.36
6.83⫾0.44
5.14⫾0.55
Distensibility, mmHg⫺1 ⫻ 10⫺3
Wistar
SHR
6.40⫾0.48
7.12⫾0.33
5.91⫾0.31
6.70⫾0.42
Distensibility, mmHg⫺1 ⫻ 10⫺3
Wistar
SHR
7.61⫾1.09
8.42⫾1.10
Adjusted for weight
2.60⫾1.36
1.63⫾0.52
Adjusted for MAP
3.00⫾0.28
4.35⫾0.52
Adjusted for weight and MAP
6.17⫾0.37
7.07⫾0.51
1.70⫾1.09
4.21⫾0.53
Values are means ⫾ SE. Note that distensibility was reduced with age whatever the type of adjustment. Adjustment to body weight tended to increase
distensibility, but only at 5 and 12 wk. Adjustment to MAP or to MAP and body weight produced higher distensibility in SHR than in Wistar rats at each given
value of age, whereas opposite results were observed using nonadjusted parameters. P1, P value for age effect; P2, P value for strain comparison; P3, P value
for interaction.
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Wistar rats (P2: strain effect) and, in each strain, increased
significantly with age (P1: age effect). A significant interaction
(P ⬍ 0001) between strain and BP was observed but only for
pulsatile pressure. From 12 to 78 wk, the pulsatile pressureto-MAP ratio increased more (P ⬍ 0.0001) in SHR than in
Wistar rats (Fig. 2).
Nonadjusted operational distensibility was significantly
lower in SHR than in Wistar rats (P ⬍ 0.0001) and, in each
strain, was significantly reduced with age (P ⬍ 0.0001) (Table
1). This reduction in operational distensibility was due to a
reduction in pulsatile diameter and an increase in pulsatile
pressure.
Table 2 shows the values of carotid distensibility as a
function of age before and after adjustment of (successively)
body weight, MAP, and body weight and MAP. In all three
models, distensibility was reduced with age independently of
strain. After adjustment to MAP and body weight, CCA pulsatile diameter and distensibility were not different between the
two strains and were even higher in SHR than in Wistar rats at
each given value of age (Fig. 3). No significant interaction was
observed (Fig. 3).
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ADJUSTED DISTENSIBILITY IN SHR
Table 3. Abdominal aorta: nonadjusted values for hemodynamic parameters according to age and strain
Age, wk
SBP, mmHg
DBP, mmHg
MAP, mmHg
PP, mmHg
HR, beats/min
Mean diameter, ␮m
Distensibility, mmHg⫺1 ⫻ 10⫺3
12
52
78
101.9⫾6.8
145.3⫾7.3
67.9⫾5.6
107.8⫾6.1
83.0⫾6.0
124.0⫾6.5
34.0⫾2.6
37.8⫾2.8
381.4⫾14.5
378.8⫾15.7
0.78⫾0.05
0.89⫾0.05
9.3⫾0.6
5.2⫾0.6
6.03⫾0.57
3.18⫾0.61
134.4⫾6.3
147.4⫾6.8
98.5⫾5.3
109.7⫾5.6
113.3⫾5.6
126.4⫾6.0
35.9⫾2.4
37.7⫾2.6
333.4⫾13.6
318.4⫾14.5
1.33⫾0.05
1.16⫾0.05
5.1⫾0.5
5.2⫾0.6
3.61⫾0.53
2.91⫾0.57
137.0⫾4.1
185.4⫾6.3
99.1⫾3.4
136.0⫾5.3
114.1⫾3.6
157.6⫾5.6
37.9⫾1.6
49.5⫾2.4
320.7⫾8.8
314.0⫾13.6
1.67⫾0.03
1.53⫾0.05
4.5⫾0.4
4.1⫾0.5
3.26⫾0.34
1.76⫾0.53
132.9⫾5.2
208.4⫾6.3
96.2⫾4.3
157.3⫾5.3
112.1⫾4.6
174.3⫾5.6
36.6⫾2.0
51.3⫾2.4
1.29⫾0.04
1.80⫾0.05
4.6⫾0.4
4.5⫾0.5
2.70⫾0.43
1.35⫾0.53
P1
P2
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0001
⬍0.0005
0.0006
0.0001
0.02
0.02
0.99
0.9 (NS)
⬍0.0001
0.03
⬍0.0001
⬍0.0001
0.003
0.02
0.0002
0.4 (NS)
0.0003
P3
Values are means ⫾ SE. P1, P value for age effect; P2, P value for strain comparison; P3, P value for interaction.
tion were observed (data not shown). Figure 4 illustrates the
result for pulsatile diameter.
On the basis of the overall data, it is worth noting that the
reduction in distensibility with age was more pronounced for
the CCA than for the abdominal aorta, whether adjusted or
nonadjusted values are considered.
DISCUSSION
This study investigated the CCA and abdominal aortic distensibilities measured at different ages in operational conditions in SHR compared with distensibilities of Wistar normotensive rats. Without adjustment to body weight and MAP,
CCA and abdominal distensibilities were reduced in SHR
compared with controls and also were markedly reduced with
age, mostly for CCA. After adjustment to MAP and body
weight, CCA and abdominal distensibilities were reduced with
age to the same extent as without adjustment, whereas normotensive and hypertensive animals achieved the same level of
distensibility (or even higher values in hypertensives than in
normotensives for CCA). The results indicate that, whereas age
clearly reduced arterial function, hypertension had a different,
and possibly opposite, effect on the mechanical properties of
large arteries in SHR.
Previously, the viscoelastic properties of the large arteries
were studied exclusively in vitro, and only the changes in
Fig. 4. Abdominal aorta study: mean values of pulsatile diameter (%) adjusted
for body weight and MAP, according to age and strain in SHR (E) and Wistar
rats (■). The degree of significance is indicated. For simplicity, SE are not
indicated.
AJP-Heart Circ Physiol • VOL
calculated steady-state arterial diameter vs. changes in steadystate transmural pressure were determined (3). Transmural
pressure was measured with a wide range of both operational
and nonoperational pressures. Presently, echo-tracking techniques of high resolution are used, and these have been extensively validated in vivo in both humans and small rodents (1,
20, 22, 26). Pulsatile pressure and diameter are determined
locally using exclusively operational measurements, thus enabling a local (carotid and abdominal aorta) evaluation of
vascular elasticity with a high degree of reproducibility. Our
group (1, 12, 22, 26) previously showed that in rodents anesthesia did not consistently alter the results. Particularly, when
distensibility was compared in normotensive and hypertensive
populations, very close results were observed under anesthesia
(SHR and Wistar rats) or without anesthesia (normotensive and
hypertensive humans) (9). Furthermore, we extensively
showed that the experimental procedure did not alter the local
carotid innervation and that baroreflex denervation was modified in a quite different extent for arterial structure and function
(6, 7). The principal limitation of the present methodology was
that, in rats, distensibility measurements in the distal aorta
require an abdominal incision, a procedure that modifies per se
the BP level. Thus the carotid and abdominal aorta data should
be presented independently and should require separate statistical evaluations. However, despite such difficulties, a similar
interpretation of the results could be observed at both the CCA
and abdominal aorta site.
In both strains, operational distensibility was progressively
reduced with age, with a more pronounced effect on the CCA
than on the distal aorta territory (Tables 1 and 2). The finding
was identical before and after adjustment for body weight and
operational MAP. However, whereas nonadjusted operational
distensibility was significantly reduced in SHR compared with
Wistar rats, this reduction completely disappeared after adjustment to body weight and MAP, and distensibility reached
values very similar in normotensive and hypertensive animals.
These findings indicate that age and MAP have different and
even potentially opposite effects on arterial function. Other
research groups (1, 9, 12, 22, 26) used the same experimental
procedures to evaluate arterial function but different mathe-
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Pulsatile diameter, %
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
Wistar
SHR
5
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ADJUSTED DISTENSIBILITY IN SHR
AJP-Heart Circ Physiol • VOL
ventricular-aortic coupling, particularly at an early period of
life. Whether such mechanisms interfere later within the lifespan of SHR requires further investigations.
ACKNOWLEDGMENTS
We thank Anne Safar for fruitful discussions.
GRANTS
This study was performed with the help of Institut National de la Santé et
de la Recherche Médicale and Groupe de Pharmacologie et d’Hémodynamique
Cardiovasculaire, Paris.
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14. O’Callaghan CJ and Williams B. The regulation of human vascular
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Stiffness of capacitive and conduit arteries: prognostic significance
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16. Radaelli A, Mircoli L, Mancia G, and Ferrari AU. Nitric oxidedependent vasodilation in young spontaneously hypertensive rats. Hypertension 32: 735–739, 1998.
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matical models for statistical evaluations. They obtained quite
similar results using follow-up of shorter duration. Previously,
our group (11) reported that, in SHR and Wistar rats, when
baseline carotid compliance was plotted vs. transmural pressure using an “in vivo in situ” model, the maximal value of
operational carotid compliance exactly corresponded to the
level of operational MAP of each particular strain. Together,
all of these findings suggest that the level of operational MAP
in SHR might contribute to maintain or even somewhat optimize arterial function at any given value of age.
Because sympathetic overactivity is a classical and early
hallmark of SHR (4), it is worth evaluating in such animals the
possible links between autonomic nervous system, arterial
distensibility, and structure and function of the aortic wall.
Regarding endothelial function, others and we have shown
that, in young SHR, an upregulation of nitric oxide is observed
(2, 5, 11, 16). This process contributes actively to optimize
arterial distensibility in young animals, despite the presence of
sympathetic hyperactivity. Thus nitric oxide, which is known
to increase arterial distensibility per se, may be considered as
contributing to maintenance of large artery function in SHR
(20). Regarding structural changes of the medial vessel wall,
aortic hypertrophy and the development of extracellular matrix
are classical features in SHR (9, 12, 19). Recent studies of
human vascular smooth muscle cells have shown that adrenergic stimulation directly modulates transforming growth factor-␤1 growth factor expression, fibronectin, and extracellular
matrix protein synthesis of elastin and collagen of the arterial
wall (14, 23, 25).
It is well established that, in humans and rodents around
birth, cardiovascular survival requires not only an adequate
pulmonary function but also an efficient ventricular-aortic
coupling to respond to the peripheral oxygen needs of the
tissues. For this purpose, and particularly because the cardiac
pump is intermittent and often upregulated at birth, an adequate
buffering function of the aorta is rapidly needed. An efficient
windkessel function should involve 1) an effective development of aortic elastic tissue and 2) a MAP level susceptible to
optimize the ventricular-aortic coupling and therefore to minimize pulsatility (13, 21, 24). Because MAP, in the presence of
increased cardiac function, depends on vascular resistance, i.e.,
on the development of small arteries and arteriolar bifurcations
at the peripheral level, only a long-term process of progressive
increase of MAP is able, during vascular development, to
optimize windkessel function (10, 19). Such observations
might explain why, at birth, an efficient autonomic nervous
system should play a major role on cardiac-aortic coupling
(18). From this viewpoint, it is worth noting that, very early
during development (18, 21), 1) tenso-receptors are mainly
located within the carotid and the initial portion of the thoracic
aorta vessel wall, 2) cardiovascular smooth muscle cells are
mainly issued from ectoderm and neural crest (17, 19, 23), and
3) the growth of neural axons and growth of central arterial
vessels are influenced by similar biochemical mechanisms of
guidance (10).
In conclusion, the present study has shown that in SHR, after
adjustment to MAP and body weight, carotid and aortic distensibilities do not differ from those of normotensive controls
and might contribute to optimize aortic elasticity. This process
requires coordinate changes of MAP and cardiovascular tissue
to maintain an adequate windkessel function and an efficient
ADJUSTED DISTENSIBILITY IN SHR
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