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Morphology of the carotid sinus wall in normotensive and spontaneously hypertensive rats.

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THE ANATOMICAL RECORD 218:426-433 (1987)
Morphology of the Carotid Sinus Wall in
Normotensive and Spontaneously
Hypertensive Rats
JOHN T. HANSEN
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and
Dentistry, Rochester, NY 14642
ABSTRACT
The morphology of the carotid sinus region of the internal carotid
artery was studied in spontaneously hypertensive rats (SHR) at 5, 8, 16, and 24
weeks of age. The carotid sinus region occupied the proximal millimeter of the
internal carotid artery, and was easily recognizable by the presence of a n extensive
adventitial capillary plexus, which was absent on adjacent arteries (e.g., common
and external carotid arteries). Methylene blue-stained whole-mount preparations
showed the extent of baroreceptor nerves over the sinus. Baroreceptor fibers terminated in distinctive bulbous-like endings, which, at the ultrastructural level, were
filled with mitochondria. No differences were noted in the sinus adventitial capillary
network or baroreceptor distribution between SHR and age-matched Wistar-Kyoto
(WKY) normotensive control animals. With the onset of a significant rise in SHR
blood pressure, the carotid sinus wall increased in thickness and total vessel size.
The w a l l h m e n ratios were significantly larger in the SHR than in age-matched
WKY ratios in all age groups. SHR carotid sinus vessel enlargement was uniform
throughout the vessel tunics, with no significant change in the proportion of the
tunica media occupied by smooth muscle cells. The increase in the carotid sinus wall
thickness associated with increasing hypertension could affect the ability of the
sinus to distend and may play a secondary role in the maintenance of hypertension
by compromising baroreceptor nerve ending sensitivity.
The spontaneously hypertensive rat (SHR) is frequently used as a n animal model of human essential
hypertension. A number of factors contribute to the development and maintenance of hypertension in this animal, including a variety of neurogenic factors involving
both the central and sympathetic nervous systems (Okamoto et al., 1967; Judy et al., 1976), structural alterations in the blood vessels (Warshaw et al., 1980; Lee et
al., 1983a), and a loss of baroreceptor reflex control of
sympathetic nervous activity (Brown et al., 1978; Judy
and Farrell, 1979). Because of the intimate relationship
between the baroreceptor nerve endings and carotid
sinus wall, any structural alterations that may occur in
the sinus wall can alter baroreceptor sensitivity. In fact,
several groups have suggested that baroreceptor resetting is due to a reduced vessel distensibility andlor
changes in the baroreceptor endings themselves (Andresen et al., 1978; Nosaka and Wang, 1979). In the present
study, the morphology of the carotid sinus region of the
internal carotid artery was examined in normotensive
Wistar-Kyoto (WKY) and SHR rats to determine if alterations in the sinus occurred that might alter normal
baroreceptor functioning.
0 1987 ALAN R. LISS, INC.
MATERIALS AND METHODS
Animals
Experiments were performed on male SHR and WKY
rats from the Okamoto-Aoki strain obtained from
Charles River Breeding Laboratories. Rats were studied
a t 5,8,16, and 24 weeks of age. All animals were housed
in animal rooms on a 14:lO LD cycle with temperature
maintained a t 75 2°F at 50% relative humidity. Systolic blood pressure was determined in conscious rats by
a photoelectric tail cuff pulse detector (IITC, Inc., Landing, NJ). Animals were conditioned to the restraining
cages prior to pressure measurements, and mean systolic pressure was determined from 4 or 5 pressure measurements. Systolic blood pressures were obtained on
the afternoon of the day before sacrifice.
Vascular Casts
Three to five SHR and WKY rats at each age interval
(5, 8, 16, and 24 weeks) were anesthetized with sodium
Received November 26, 1986; accepted March 6, 1987
CAROTID SINUS WALL IN HYPERTENSION
pentobarbital (40 m g k g i.p.1 and perfused through the
heart with warm (30°C) saline containing 1,000 units of
heparin per 500 ml. Perfusion pressure was maintained
a t 80% of the mean systolic blood pressure (Hart et al.,
1980) by adjusting the height of the fluid bottles in our
gravity perfusion system. When the effluent from the
incised right atrium was clear (about 30-60 sec), the
rats were perfused with a warm (30°C) fixative solution
containing 3% glutaraldehyde in 0.1 M sodium phosphate buffer a t pH 7.2. Each animal was infused with
200 ml of fixative. Immediately following the perfusion,
Mercox (Ladd Research Industries, Burlington, VT) was
prepared by combining 20 ml of resin with 1 ml of
catalyst in a 50-ml syringe. Mercox is a low-viscosity
methacrylate resin used for preparing corrosion casts of
the vasculature. The Mercox mixture was infused
through the heart and into the ascending aorta in 1min,
by which time the resin had begun to polymerize. The
infused rat was cured for 1 h r in a n oven at 50°C, and
then the desired area of the carotid bifurcation was
removed. These samples were macerated in 5.25% hypochlorite (household bleach) for 24-48 hr. Once clean of
soft tissue, the casts were rinsed in distilled water, airdried, oriented, and mounted on scanning electron microscopy stubs, sputter-coated with gold, and examined
in a scanning electron microscope at 15 kV. Appropriate
casts were photographed on Polaroid Type 55 film (ASA
50).
Methylene Blue Staining
The distribution of the carotid sinus baroreceptor
nerves over the carotid sinus region of the internal carotid artery was studied in whole-mount preparations
stained with methylene blue (Richardson, 1969; McDonald, 1983). Five or six WKY and SHR rats at 5, 8,
and 16 weeks of age were studied. The rats were anesthetized with sodium pentobarbital (40 m g k g i.p.) and
injected intravenously with heparin (250 units). Then
the rats were perfused with 0.9% NaCl via the left
ventricle for 1min at 120 mm Hg, followed by 1 liter of
0.01% methylene blue chloride in phosphate buffer at
pH 5.0 for 10 min. Prior to the perfusion, the methylene
blue chloride solution was equilibrated with 100% 0 2 by
bubbling the oxygen through the solution. When the
perfusion was finished, the carotid bifurcations were
removed immediately and immersed in ammonium molybdate fixative at 4°C for 6-24 hr (Richardson, 1969).
Specimens consisting of the carotid sinus, carotid body,
and superior cervical ganglion were rinsed in water,
flattened between two glass slides in 100% methanol,
dehydrated in methanol, cleared in xylene, mounted as
whole mounts on slides, and coverslipped with Permount. The linear extent of the carotid sinus nerve
innervation from caudal to rostra1 on the sinus portion
of the internal carotid artery was measured in the light
microscope a t 40 x with a n ocular reticule.
Light and Electron Microscopy
WKY and SHR rats at each age interval were anesthetized with sodium pentobarbital(40 m g k g i.p.1 and their
carotid bifurcations (4 to 6 bifurcations per age group)
were fixed for light and electron microscopy by intracardiac perfusion of a solution containing 3% glutaraldehyde in 0.076 M cacodylate buffer with 60 mM H202, 2
mM CaC12, 30 mM sucrose, and 1 mM polyvinylpyroli-
427
done (pH 7.2, room temperature, 520 mOsmol). The fixative was preceded by a saline flush (50 ml), and pressure
was controlled by gravity a t 80% of the mean systolic
pressure (Hart et al., 1980). Subsequent morphological
examination verified that all vessels were fixed in a
fully dilated (relaxed) state, as evidenced by the stretched
internal elastic lamina, rounded smooth muscle cell nuclei, and smooth plasma membrane, typical of relaxed
smooth muscle cells. Following a 10-min perfusion, the
carotid bifurcation was removed and immersed in fresh
fixative for a n additional 4-6 h r at 4°C. The carotid
sinus region of the proximal internal carotid artery was
sectioned transversely into a small piece about 1 mm
long and washed in cacodylate buffer overnight. The
tissue samples were postfixed in 1.5%osmium tetroxide
in 14 mM Verona1 acetate-HC1 buffer (pH 7.4) for 1 hr
a t room temperature. The samples were then stained en
bloc with 1.5%uranyl acetate in 25 mM maleate buffer
(pH 5.0) for 6 h r a t room temperature, dehydrated in
acetone, and embedded flat in Spurr's plastic in aluminum weighing pans. The specimens then were sawed
from disks of the polymerized resin, oriented, and
mounted on transparent acrylic cylinders (7.9 mm x
12.7 mm) with cyanoacrylate adhesive. Sinus regions
were oriented so that sections could be cut transversely
across the vessel.
For light microscope examination, 1-pm sections were
cut from the center of the sinus and stained with toluidine blue. These sections were coverslipped and photographed in the light microscope. For electron microscopy,
thin sections (70 nm) were cut with a diamond knife on
a n ultramicrotome, and collected on 50-mesh formvarcarbon-coated grids. Thin sections were stained on grid
with lead citrate and examined in the electron microscope at 60 kV.
Morphometric Analysis
For light microscope analysis, 1-pm plastic sections
were photographed and enlarged on photographic paper
. standard morphometric apto either x 140 or ~ 2 0 0By
proaches (Weibel, 1979), each carotid sinus was measured on a Zeiss MOP-3 digitizing pad (Car1 Zeiss, Inc.,
New York, NY) and the data were recorded. The prints
were coded so that the observer collecting the data was
unaware of group identity. Estimates of wall thickness
(collected at 12 equidistant points around each vessel),
vessel perimeter and area (tunica intima and media),
and lumen perimeter and area were collected directly
by tracing over the structures with the digital image
analyzer. Significant differences between age-matched
WKY and SHR samples were determined by a Student
t test. A probability of P<O.O5 was chosen as the level
of significance.
At the ultrastructural level, morphometric data on the
baroreceptor nerve endings were not collected, although
their general features are described in Results. Morphometric data were collected on the features of the carotid
sinus wall. Each of four or five carotid sinus samples
from each group of rats was photographed across the
entire thickness at two different locations. The first complete sections encountered in the electron microscope
were used for sampling. Micrographs were taken a t low
magnifications ( x 2,000) and photographically enlarged
to ~ 5 , 0 0 0The
.
fractional volume Wv) of smooth muscle
cells and the extracellular compartment (largely colla-
428
J.T. HANSEN
gen and elastic components) were estimated by pointcounting techniques (Weibel, 1979). A transparent overlay with 63 points was used to collect the data from each
8-in x 10-in print. The data were pooled from each sinus
and the values averaged to determine a group average.
Data were expressed as percentage of the tunica media
occupied by smooth muscle or the extracellular compartment. Significant differences between age-matched
WKY and SHR samples were determined by a n ANOVA. A probability of P< 0.05 was chosen as the level of
significance.
RESULTS
The mean systolic blood pressures and body weights
a t the time of sacrifice of the WKY and SHR groups a t
5 , 8, 16, and 24 weeks of age are shown in Table 1. The
mean systolic blood pressure in the SHR was already
significantly elevated a t 5 weeks of age compared to the
age-matched WKY animals. From 16 weeks of age and
older, the SHR body weight was significantly greater
(P<O.OOl) than that of the normotensive WKY rats.
TABLE 1. Mean systolic blood pressure and body weight'
Group
WKY-5
SHR-5
P
WKY-8
SHR-8
P
WKY-16
SHR-16
P
WKY-24
SHR-24
P
Body weight
(gm)
Blood pressure
(mm Hg)
111.6 f 20.5
129.4 f 15.8
0.02
117.8 f 11.3
136.7 f 8.7
0.001
116.9 f 8.9
150.8 f 26.1
0.001
107.8 f 8.9
164.2 f 24.4
0.001
N
86.5 f 10.9
74.4 f 11.1
0.01
180.9 f 15.6
174.4 f 20.1
NS
242.4 f 9.5
304.8 k 10.4
0.001
289.8 f 8.1
372.1 f 7.0
0.001
15
14
16
15
16
15
6
6
'Values are means k standard deviations of each group of 5, 8, 16,
and 24 weeks of age. P values compare WKY rats with their agematched SHR.
General Morphology
The carotid sinus region in both WKY and SHR occupied the proximal millimeter of the internal carotid artery. The distal common carotid artery was a transitional
artery (Simionescu and Simionescu, 1983), which displayed both prominent elastic lamellae and well-defined
bands of smooth muscle (Fig. 1). Although the elastic
lamellae appeared thinner than those of the common
carotid artery, the proximal portions of the external and
internal carotid arteries also were transitional arteries,
that is, they possessed histological features intermediate between elastic and muscular arteries (Figs. 2
and 3).
The carotid sinus in the WKY and SHR was easily
recognizable by the presence of a capillary plexus in its
tunica adventitia (Figs. 3 and 4). The capillaries were
not observed penetrating the tunica media, so the identification of this adventitial network as true vasa vasorum is questionable. No other region of the adjacent
common, external, or internal carotid arteries possessed
this capillary network. This adventitial, or perivascular,
network of capillaries appeared to originate from small
arterioles of the adjacent carotid body chemoreceptor
(Fig. 4). Several larger venules also were present and
presumably drained the carotid body and sinus capillaries.
Baroreceptor Morphology
The carotid sinus region also was fairly well delineated in methylene blue-stained whole-mount preparations. Nerve axons were observed over the entire extent
of the sinus region but were most abundant over the
dorsolateral aspect of the sinus. These presumptive
baroreceptor fibers terminated in bulbous endings when
stained with methylene blue (Figs. 5 and 6). Often, one
or two axons gave rise to several secondary branches
that terminated upon the sinus wall in typical bulbous
profiles (Fig. 6). Some of these axon profiles were quite
convoluted or coiled in appearance. The precise number
of carotid sinus axons terminating on the sinus wall
could not be determined because the proportion of axons
stained by methylene blue was not known. If any differ-
TABLE 2. Light microscoDe measurements of the carotid sinus'
5 Week
Wall thickness
8 Week
WKY
SHR
45.1 f 2
42.1 f 2
WKY
SHR
16 Week
SHR
WKY
40.3 f 1.5 50.0 f 1.72 40.2 f 2
54.3
24 Week
SHR
WKY
2.62 47.9 f 2.4 62.8 f 1.72
(pm)
Vessel perimeter
(10~
pm)
Vessel area
(104 pm2)
Lumen perimeter
(10~
pm)
Lumen area
(104pm2)
21.9 f 0.8 18.4 f 0.72 23.5 f 0.4 23.7 k 0.4
25.0 f 0.9 30.4 f 1.02 23.1 f 0.7 29.4 f 0.72
37.2 f 2.5 25.8 f 1.9'
42.4 f 1.4 42.9 f 1.1
47.8 f 3.3 71.8
19.2 f 0.8 16.0 f 0.6
21.1 f 0.4 20.7 k 0.4
22.5 k 0.9 27.0 k 0.g2 20.2 f 0.6 25.6 f 0.7'
28.5 f 2.2 18.9 f 1.5
33.9 f 1.2 32.4 f 0.9
38.6 f 2.6 56.5 f 3.42 31.3 f 1.9 51.0 k 2.62
Total vessel Derimeter 23.9 f 0.9 20.1 k 0.8
26.1 f 0.6 25.8 f 0.4
27.4 k 1.0 32.8 f 1.12 25.5 f 0.8 32.4 f 0.82
4.62 41.3 f 2.5 67.5 k 3.12
(10' pm)
Wallflumen ratio3
77.9 f 2.5 97.8 f 4.82 67.4 f 2.0 82.3 f 2.2'
(1n-3)
'Values are means standard error of the mean.
'P < 0.01, significantly greater than age-matched WKY.
3Wall thicknessflumen diameter.
58.8 k 1.9 70.5 f 2.62 74.1 f 2.1 87.5 f 2.2'
CAROTID SINUS WALL IN HYPERTENSION
429
Fig. 1. Light micrograph of distal common carotid artery showing a
portion of the lumen and alternating bands of smooth muscle and
elastic lamellae (el). ~ 2 2 0 .
h
Fig. 2. Micrograph of a portion of the wall of the proximal external
carotid artery. The elastic lamellae are less distinct. x220.
be
A
..-
A
B
5Oum
Fig. 3. Micrograph of a portion of the carotid sinus wall from a 16week-old WKY. Note elastic lamellae and smooth muscle cells of tunica
media. A portion of the adjacent carotid body (cb) chemoreceptor also
is visible. ~ 2 2 0 .
Fig. 4. Scanning electron micrograph showing proximal portions of
the external (ec) and internal (ic) carotid arteries. Note the distinctive
adventitial capillary network (cn) over the proximal internal carotid
artery, demarcating the carotid sinus zone. These capillaries appear to
come from the vascular network of the adjacent carotid body. Several
venules (v) also are evident in this micrograph. x 75.
Fig. 5. Light micrograph of several presumptive baroreceptor endings of the carotid sinus stained with methylene blue. Note their
bulbous endings and coiled appearance. From a 5-week-old SHR sinus.
x290.
Fig. 6. Camera lucida drawings of two methylene blue-stained wholemount preparations of presumptive baroreceptor nerve endings. Often,
one or two axons give rise to several secondary branches that are
coiled and terminate in bulbous endings.
430
J.T.HANSEN
TABLE 3. Fractional volume of tunica media occupied by
smooth muscle and extracellular components’
Smooth muscle
Group
WKY-5
SHR-5
WKY-8
SHRS
WKY-16
SHR-16
WKY-24
SHR-24
(%I
45.9
36.7
41.6
39.2
36.9
34.2
41.1
41.0
k 0.5
* 1.4
*k 7.9
1.6
f 3.2
k 4.1
f 6.7
f 2.6
Extracellular
components’
(%)
N
54.2 f 0.4
63.3 k 1.3
58.4 f 1.4
60.8 f 6.8
63.1 f 2.9
65.8 f 3.6
58.9 f 6.0
59.0 k 2.3
4
5
4
4
5
5
5
5
‘Values are means
standard error of the mean. There were no
significant differences (ANOVA).
‘Includes elastic laminae and collagen.
ences in the number or distribution of axons did exist
among the WKY and SHR groups, they were not evident
in these whole-mount preparations.
Ultrastructurally, the presumptive baroreceptor endings of the carotid sinus nerve were quite distinct. Most
axon terminals were located in the medial one third of
the tunica adventitia and possessed a n axoplasm almost
completely filled with round or oval mitochondria (Figs.
7-9). The mitochondria-filled bulbous terminals were
partially or completely surrounded by Schwann cell processes and were found within a bed of extracellular
connective tissue composed largely of collagen fibers
(Figs. 8, 9). Microtubules, a few dense-core vesicles, and
larger dense bodies (perhaps lysosomes?) also were present in the terminals (Fig. 8).Occasionally, multiple layers of the basal lamina were observed surrounding each
terminal (Fig. 10). This feature was inconsistent, but it
appeared in both WKY and SHR carotid sinus samples.
Presumptive baroreceptor terminals were never observed in the tunica media or adjacent to smooth muscle
cells. Obvious morphological differences between the
axon terminals of WKY and SHR carotid sinuses were
not noted.
Analysis of the Carotid Sinus Wall
Morphometric data gathered at the light microscope
level from the carotid sinus region are summarized in
Table 2. The wall thickness (tunica intima, media, and
adventitia) was significantly greater (P< 0.01) in the
SHR from 8 to 24 weeks of age. The carotid sinus portion
of the internal carotid artery in the SHR was significantly larger (P< 0.01) (vessel perimeter and area) at 16
and 24 weeks of age compared to the age-matched WKY.
Lumen perimeter and area also were larger in the SHR
a t 16 and 24 weeks. Across the various SHR age groups
from 5 to 16 weeks, there was a tendency for the wall
thickness, vessel perimeter and area, lumen perimeter
and area, and total vessel perimeter to increase. While
these same parameters increased in the WKY carotid
sinuses, their magnitude was much smaller. For example, vessel area and lumen area increased 162% and
170%, respectively, in the SHR from 5 to 24 weeks of
age. Over the same period, vessel area and lumen area
were increased only 11%and 10%, respectively, in the
WKY. Likewise, wall thickness increased 49% in the
SHR, but only 6% in the WKY. The wallAumen ratio of
the carotid sinus region was significantly larger in the
SHR in all age groups.
At the ultrastructural level, the fractional volume of
the tunica media occupied by smooth muscle and extracellular components (elastic lamellae and collagen) was
determined. These data are shown in Table 3. The percentage of the tunica media occupied by smooth muscle
cells tended to increase from a low of 36.7% a t 5 weeks
of age to a high of 41% at 24 weeks of age in the SHR
carotid sinus wall. However, this tendency was not significantly different from the age-matched WKY smooth
muscle fractional volume in any age group (Table 3).
DISCUSSION
The salient findings of the present investigation are
that the carotid sinus baroreceptor distribution and morphology in WKY and SHR rats are similar, but the
carotid sinus wall in the SHR is significantly thicker.
This increase in thickness probably is secondary to the
increase in blood pressure.
Morphologically, the carotid sinus portion of the proximal internal carotid artery is a transitional artery,
possessing histological characteristics intermediate between elastic and muscular arteries. The sinus region
in both the WKY and SHR, unlike the adjacent portions
of the common, internal, or external carotid arteries,
possesses a rich perivascular network of capillaries in
its tunica adventitia. McDonald and Larue (1983) have
described this unique feature of the carotid sinus in rats
of the Long-Evans strain and refer to this capillary
network as vasa vasorum. However, unlike true vasa
vasorum, which penetrates the tunica media, this “adventitial” network of capillaries is never observed
branching the media. The capillary network appears to
originate from small arterioles of the adjacent carotid
body, and accompanies branches of the carotid sinus
nerve and sympathetic fibers as they pass over the sinus
region. Baroreceptor nerve endings usually are observed
within the immediate vicinity of the capillaries, and
they may receive their blood supply through this network (McDonald and Larue, 1983; Hansen, 1985). No
obvious differences in the capillary network are evident
between the WKY and SHR carotid sinuses.
From methylene blue-stained preparations, it is clear
that the baroreceptive field encompasses the most proximal millimeter of the internal carotid artery wall. Baroreceptor endings are most prominent over the dorsolateral aspect of the sinus. A similar pattern of distribution exists in the Long-Evans rat (McDonald, 1983).
Yates and Chen (1980) described the baroreceptor field
as limited to a narrow area of about 0.5 mm wide and
covering one third to one half of the circumference of
the internal carotid artery. With methylene blue staining one is able to examine the entire sinus in a wholemount preparation; by this approach, presumptive baroreceptor endings are observed over a broader area of
the sinus wall, although by far the greatest accumulation of endings lies on the dorsolateral aspect of the
artery. The distribution in the WKY and SHR is similar.
Baroreceptor nerve endings exhibit a unique bulbous
appearance in methylene blue-stained preparations
(McDonald, 1983) that a t the ultrastructural level appear as mitochondria-packed terminals. These characteristic features are common to baroreceptor endings
described by others in a variety of species (Rees, 1967;
CAROTID SINUS WALL IN HYPERTENSION
Fig. 7.Electron micrograph of several presumptive baroreceptor
endings (b)situated in the medial one third of the tunica adventitia.
Note the adjacent external elastic lamina (ell separating the tunica
adventitia from the tunica media. Baroreceptor endings often are surrounded by processes of Schwann cells (S).Sinus wall of a 24-week-old
SHR. ~ 3 , 2 6 0 .
Fig. 8.Several baroreceptor endings in the sinus wall of a 24-weekold SHR. Note that the endings are filled with round or oval mitochondria and are surrounded by processes of a Schwann cell. Occasional
dense-core vesicles (dcv) and larger dense bodies resembling lysosomes
(lys) are present in the terminals. Collagen (col) and elastic fibers (ef)
fill the extracellular spaces. x 18,000.
431
Fig. 9.Baroreceptor ending from a n 8-week-old WKY carotid sinus.
Note several dense-core vesicles (dcv) and numerous mitochondria.
Collagen (col) lies in the extracellular space, and the ending is enveloped by a Schwann cell process (arrows). ~21,400.
Fig. 10. Portion of baroreceptor preterminal axon in longitudinal
section exhibiting microtubules (mt), and partially surrounded by a
Schwann cell process. Note multiple layers of basal lamina (bl). From
a n 8-week-old WKY sinus. ~29,750.
432
J.T. HANSEN
Bock and Gorgas, 1976; Knoche and Addicks, 1976;
Krauhs, 1979; Knoche et al., 1980; Yates and Chen,
1980; Taha et al., 1983). The baroreceptor endings in the
WKY and SHR are similar in appearance. The nerve
endings are never observed in the tunica media, but are
limited to the inner portions of the tunica adventitia in
close association with collagen and elastic fragments.
Bock and Gorgas (1976) interpret the large number of
mitochondria in the terminals as indicative of a high
metabolic rate, such as may be required by mechanoreceptors a s they respond to pressure changes. A basal
lamina surrounds the receptors and their Schwann cells
and is prominent, extensive, and multilayered in the rat
carotid sinus (Yates and Chen, 1980) and aortic baroreceptors (Krauhs, 1979).The significance of this multilayered basal lamina is unclear, although Yates and Chen
(1980) suggest that Schwann cells andor nerve terminals may lay down additional basal laminae in response
to the increase in wall tension during progressive hypertension. In this study, multilayered basal laminae, although not ubiquitous, are present in both WKY and
SHR sinus baroreceptors, regardless of blood pressure.
Moreover, Krauhs (1979) describes similar multiple layers of basal lamina in WKY and SHR aortic baroreceptors, irrespective of blood pressure. Therefore, this
feature may be a general characteristic of rat baroreceptors.
With the onset of a significant rise in SHR blood pressure, the carotid sinus wall increases in thickness,-concomitantly with a significant increase in total vessel
size. Most importantly, however, the wall/lumen ratios
are significantly larger in the SHR than in age-matched
WKY ratios in all age groups. This increase appears to
be uniform throughout the vessel wall of the SHR, since
ultrastructural analysis shows that the proportion of the
tunica media occupied by smooth muscle does not vary
significantly between the age-matched WKY and SHR
groups. However, this enlargement of the sinus wall
differs from the pattern observed on other SHR vessels.
Jurokova et al. (1976) demonstrated smooth muscle hypertrophy and hyperplasia in the aorta of rats with
short-term (3-6 months) and long-term (12-16 months)
spontaneous hypertension. Likewise, alterations are
present in mesenteric vessels, involving the muscular
and arteriolar vessels but not the elastic (superior mesenteric) ones (Warshaw et al., 1979; Lee et al., 1983a,
198313). The reaction of the carotid sinus wall to hypertension may be a result of its elastic and muscular
morphology, not being either a truly elastic or muscular
(resistance) vessel. Additional studies of other transitional arteries are needed to resolve this possibility.
Thickening of the carotid sinus wall, as observed in
this study, is dramatic, accounting for a 49% increase
between 5 and 24 weeks in the SHR, whereas the WKY
sinus wall increases in thickness by only 6%. One hypothesis of baroreceptor function suggests that the distensibility of the carotid sinus wall results in a
mechanical deformation that elicits a mechano-electrical action on baroreceptor nerve endings (Brown, 1980).
The resultant depolarization of the baroreceptors then
is transmitted to the central nervous system via carotid
sinus nerve afferents. The elastic properties of the carotid sinus wall permit this distensibility. One might
speculate that a n increase in sinus wall thickness could
compromise this mechano-electrical interaction, and result in a decrease in baroreceptor sensitivity. The increase in wall thickness probably is secondary to some
other central andor peripheral abnormality in the SHR
that precipitates the increase in blood pressure. Nevertheless, once hypertension is manifest, a n increasingly
thicker carotid sinus wall may exacerbate the hypertension further by compromising baroreceptor sensitivity.
ACKNOWLEDGMENTS
I thank Norma Peche, Albert Guzman, and Andrew
Howell for their excellent technical assistance. This
study was supported by National Institutes of Health
grant HL36038, and a Research Career Development
Award.
LITERATURE CITED
Andresen, M.C., J.M. Krauhs, and A.M. Brown (1978)Relationship of
aortic wall and baroreceptor properties during development in normotensive and spontaneously hypertensive rats. Circ. Res., 43~728738.
Bock, P., and K. Gorgas (1976)Fine structure of baroreceptor terminals
in the carotid sinus of guinea pigs and mice. Cell Tissue Res.,
170~95-112.
Brown, A. (1980) Receptors under pressure. An update on baroreceptors. Circ. Res., 46:l-10.
Brown, A.M., W.R. Saum, and S.Yasui (1978) Baroreceptor dynamics
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morphology, carotid, normotensive, wall, spontaneous, hypertension, rats, sinus
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