383s
Clinical Science (1982)63.3839-385s
Anatomical and physiological aspects of cardiovascular
function in Wistar-Kyoto and spontaneously hypertensive rats
at birth
S A R A H D. G R A Y
Department of Human Physiology, School of Medicine, University of Calfornia, Davis, CA, U S A .
Summary
1. The present study was designated to determine whether there are any detectable differences
in cardiovascular anatomy or physiology between Wistar-Kyoto (WKY) and spontaneously
hypertensive rat (SHR) pups at birth.
2. It was found that mean arterial pressures
were significantly higher, heart rates were slightly
higher, and heart weight/body weight ratios were
higher in SHR.
3. Vascular dimensions were determined in a
small sample of those rats, and the data there also
indicate hypertrophy to some degree: the ratio
of wall thickness/lumen radius was higher in
SHR, tangential wall tension and number of cell
layers in the media were increased.
4. It is concluded that some of the concomitant features of hypertension, such as left
ventricular wall hypertrophy and arterial wall
hypertrophy, may be genetically determined to
some extent in SHR.
Key words: blood vessels, heart, vascular
changes, ventricle.
Introduction
The original studies on the development of high
arterial pressure in the spontaneously hypertensive rat (SHR) [ l , 21 referred to a ‘prehypertensive’ period encompassing the first
40-50 days of age, when systolic pressure
reached 147 mmHg as compared with 131
mmHg in the normotensive control. Until recently, the ‘prehypertensive’ period has been viewed
as a period in which SHR pressures were not
greatly different from those of Wistar-Kyoto
Correspondence: Dr Sarah D. Gray, Department of
Human Physiology, School of Medicine, University of
California, Davis, CA 95616, U.S.A.
(WKY) rats until late in that period, when they
started to rise. A brief report by Bruno et d [ 3 1
showed that SHR and WKY are physiologically
ditrerent long before they are 7 weeks of age.
They, as well as others 141, have reported increased pressure and heart rate in neonatal SHR.
It is not known, however, at what age hypertrophy of the left ventricle and arterial vessels, the
characteristics of hypertension in the adult phase,
occur and whether hypertrophy is a completely
adaptive response to the pressure, or whether it is
partially genetically determined. The present
study attempts to pinpoint the developmental
aspect of hypertrophy in the SHR by determining whether there is any evidence of arterial
or ventricular hypertrophy at birth.
Methods
WKY and SHR pups were studied between hours
12 and 24 after birth. Sodium pentobarbital (15
mg/kg; half the adult dose), in a volume of 0.05
ml, was injected intraperitoneally in 24 WKY
and 23 SHR pups. They were put in a plastic
temper ature-controlled chamber (set to keep skin
temperature at 34OC, which was continually
monitored, since neonates are highly sensitive to
temperature) under a stereozoom dissecting
microscope; electrocardiogram pin electrodes
were attached to the limbs and heart rate was
recorded. The neck region was dissected with
micro-instruments and the carotid artery was
freed from the surrounding tissue; a 6-0 silk
suture was placed under the vessel and a pool of
warm Ringer solution bathed the artery.
Mean pressure was measured by piercing the
vessel with a micro-pipette filled with heparinized
T-1824 dye and connected to a pressure source
(rubber bulb) and a water manometer; the
placement of the micro-pipette was aided by use of
a micromanipulator. As soon as the vessel is
S. D.Gray
384s
TABLE1. Anatomical and physiological data from I-day-oldrats
Results are means k SEM for n animals.
SHR 23
W K Y 24
n
0.0245 f 0.001
0.0207 f 0.0012
4.74 _+ 0.17
5.06 f 0.12
52k I
40 2 2
Radius (R)
Wall thickness
(W)!irm)
WIR
16.10 f 0.58
12.I9 f 1.28
0.1439 f 0.0014
0. I076 f 0.012
(m)
SHR 5
WKY 5
11243l f 4.42
113.79 3.41
pierced, pressure is raised rapidly to 60-65 cm
water and then gradually allowed to fall by
controlled release of pressure from the bulb, and
the movement of dye into the bloodstream is
observed under the microscope. With the gradual
fall in pressure, the stream of dye decreases and
finally pressure matches that of the blood, when
dye no longer leaves the pipette. That point is
noted on the manometer. The procedure was
repeated five times on each pup and the values
were averaged.
After pressure measurement, the vessel in a
small group of animals was superfused with
Karnovsky’s fixative, in situ. This was done to
ensure that it would be fixed at the prevailing
blood pressure, as evidenced by the appearance
of the smooth muscle fibres and elastic laminae in
the media: they were long and thin, due to the
stretching by the blood pressure, as opposed to
being rounded and curled in a freely contracting
vessel. The heart was stopped in diastole by a
small injection of concentrated KCI. Both heart
and blood vessels were removed and stored in
fixative. Vessels were embedded in plastic and cut
at 1 pm thickness. Dimensions were measured on
photographs and analysed with the aid of the
Videoplan computer to determine radius (of an
equivalent circle, since the vessels were somewhat elliptical in many instances) and wall
thickness (media). The ratio of wall thickness to
lumen radius, and tangential wall stress, were also
calculated.
287.9 2 6.6
273.9 f 7.6
30.83 ? 0.91
24.15 f 0.97
10-5 x
No. of
lamellae
Wall tension
(dynelcm’)
3.01
2.86
5
4
Discussion
Most of the parameters measured or calculated
showed significant differences (at the 95% confidence level) between SHR and WKY rats. On
the day of birth, the pressures were higher, and
the ventricle weight was greater in absolute terms
as well as in relation to body weight, which is
even more remarkable because the SHR tended
to be slightly smaller in body weight, although
not significantly so. The heart rates were higher
also, but not at the same level of significance. The
carotid artery lumen size was similar in both
animals, but medial thickness was greater in
SHR; W/R ratios were also greater. Tangential
tension, which is related to the prevailing pressure, wall thickness and lumen radius, was also
higher in SHR. The number of laminae seen on
vessel cross-sections were also higher in SHR,
meaning that there was an extra layer of cells in
the SHR media.
These data indicate that at birth there are
already anatomical and physiological differences
between SHR and WKY related to the hypertensive state. These differences may indicate that
there is no true ‘prehypertensive’ period, and that
those differences may be genetically determined
in the foetus, rather than adaptively determined
by the rising pressure. These data tend to confirm
the idea expressed by Yamori et al. I51 that
hypertrophy in genetic hypertension occurs early
in the hypertensive process and that the occurrence of ventricular hypertrophy can be correlated with arterial hypertrophy.
Results
Table 1 summarizes the anatomical and physiological data on heart rate, blood pressure,
ventricular weightlbody weight ratio, carotid
artery radius ( R ) and medial wall thickness ( W ) ,
tangential wall stress (tension) and the number of
lamellae present in the media of 1-day-old
animals.
Acknowledgment
This study was supported by the California Heart
Association.
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