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Exp. Anim.

53(1), 6772, 2004


Note

Age-Related Changes in Blood Pressure, Hematological


Values, Concentrations of Serum Biochemical
Constituents and Weights of Organs in the
SHR/Izm, SHRSP/Izm and WKY/Izm

Satoshi FUKUDA1), Satoru TSUCHIKURA2), and Haruzo IIDA1)

1)International
Space Radiation Laboratory, National Institute of Radiological Sciences, 491,
Anaganwa, Inage-ku, Chiba-shi, Chiba 263-8555 and 2)Disease Model Cooperative
Research Association, 351, Aoihigashi, Hamamatsu, Shizuoka 433-8114, Japan

Abstract: Age-related changes in hematological values, serum biochemical constituents,


and weights of various organs in both sexes of the Spontaneously Hypertensive (SHR/Izm),
Stroke-prone SHR (SHRSP/Izm), and Wistar Kyoto (WKY/Izm) rat strains, bred under SPF
conditions, were examined to obtain fundamental data. The body weights from 330 weeks
and systolic blood pressure from 630 weeks in each strain were measured every week. At
the ages of 8, 16, and 30 weeks, the hematological values (erythrocyte, hemoglobin,
hematocrit, leucocyte, thrombocyte), serum biochemical constituents (total protein, GOT,
GPT, ALP, BUN, creatinine, glucose, total Ca and phosphorus, and ionized Ca, Na, K, and
Cl were measured. Also, the organs, brain, heart, lung, thymus, liver, spleen, pancreas,
bilateral kidneys, adrenal glands, testes/ovaries, digestive tract, and muscle (soleus) were
weighed. The age-related changes as well as the strain and sex differences in each
measured item were examined. The body weights of each strain increased, but rate of the
increase was less in SHR and SHRSP, and was lowest in SHRSP. The blood pressure of
SHR and SHRSP elevated with age, and showed higher in SHRSP than SHR, while that of
WKY did not change. There were many strain differences in most measured items at each
time point, particularly at 30 weeks. In SHRSP, high values of BUN, creatinine, total and
ionized Ca, weights of brain, heart, liver, kidney and digestive duct were observed at most
time points indicating that this strains abnormality of calcium metabolism may be related to
functions of the kidney and digestive duct as well as hypertension.
Key words: spontaneously hypertensive rat (SHR/Izm), stroke-prone SHR (SHRSP/Izm),
wistar Kyoto (WKY/Izm)

(Received 23 July 2003 / Accepted 16 September 2003)


Address corresponding: S. Fukuda, International Space Radiation Laboratory, National Institute of Radiological Sciences, 491, Anaganwa,
Inage-ku, Chiba-shi, Chiba 263-8555, Japan
68 S. FUKUDA, S. TSUCHIKURA AND H. IIDA

The spontaneously hypertensive rat (SHR/Izm) and


stroke-prone SHR (SHRSP/Izm) and Wistar Kyoto
(WKY/Izm) rats are widely using for the study of hy-
pertension [7]. SHR was separated from WKY in 1959
and established as an inbred strain to induce spontane-
ous hypertension in 1971. SHRSP was separated from
SHR in 1966 and established as an inbred strain to
induce spontaneous cerebral apoplexy in 1973. WKY
was established as an inbred strain in 1971. We have
also found that in SHRSP in particular osteoporosis
occurs spontaneously [1, 5, 6]. There are few anatomi-
cal and physiological data for these strains, therefore
we measured body weight weekly from 330 weeks Fig. 1. Body weights of male and female WKY/Izm, SHR/Izm,
and blood pressure from 630 weeks, and hematologi- and SHRSP/Izm rats from 330 weeks of age. Values are
cal and serum biochemical values, and weights of organs mean SD.
at the ages of 8, 16 and 30 weeks in male and female
SHR, SHRSP, and WKY rats.
The animals used were as follows: 32 males and 32 oxaloacetatic transaminase (GOT), glutamic pyruvic
females each of the WKY and SHR strains, and 35 transaminase (GPT), alkaline phospatase (ALP), blood
males and 36 females of the SHRSP strain bred under urea nitrogen (BUN), creatinine, and glucose were ob-
SPF conditions in the Laboratory of the Disease Model tained by an autoanalyzer (Express Plus, Ciba-Corning
Cooperative Research Association. The breeding room Diagnostics, USA). Total calcium was obtained by the
was kept at a controlled temperature of 22 2C and a o-cresolphtalein complexone method and phosphorus
relative humidity of 55 5%, with a 12-h dark-light by the molybdenum blue method (Calcium C-test kit,
cycle. Rats were given Funabashi SP diet containing and Phospher B-test kit, Wako Pure Chemical Indus-
1% NaCl (Funabashi Farm Co.) and distilled water tries, Ltd., Japan). Ca2+, Na+, K+, and Cl were obtained
freely. by an ion electrode method (Sera series, Horiba Ltd.,
The body weights of rats were measured by balance Japan), respectively.
(PE-6000, Mettler Ltd., Japan). Blood pressure was Organs such as the brain, heart, lung, thymus, liver,
measured by the tail-pulse pickup method (UR-5000, spleen, pancreas, bilateral kidneys, adrenal glands, tes-
Ueda Co. Ltd.). Blood was drawn from the caudal tes/ovaries, and digestive tract (from esophagus to
vena cava under anesthesia by chloroform and divided colon) and skeletal muscle (soleus) were extracted, and
into two tubes. One tube for hematological examina- fat was completely removed. The weights of organs
tion was used immediately after blood collection. were measured by balance (AE-100, Mettler Ltd., Ja-
Another tube was centrifuged at 3,000 rpm for 15 min pan).
to obtain serum, and the ionized calcium (Ca2+), so- Statistical analyses were performed by one-way
dium (Na +), potassium (K+) and chlorine (Cl) were ANOVA test and the Students t-test. A value of p<0.05
measured just after serum separation, with the remain- was considered statistically significant.
ing serum being frozen at minus 20C for later The body weights of both sexes in each strain in-
biochemical analyses. creased rapidly from 3 weeks to 810 weeks and then
The measured items and methods were as follows. continued to increase gradually to 30 weeks (Fig. 1).
Hematological examinations for erythrocytes, hemoglo- In the males, the differences in body weights of the
bin, hematocrit, leucocytes, and thrombocytes were three strains were enlarged after 89 weeks, and the
performed with a blood cell counter (Sysmex K-1000, values (mean SD) in the SHR, SHRSP and WKY rats
TOA Co., Japan). Serum total protein was obtained by at 30 weeks were 405 19 g, 334 29 g, and 464 14
a physical meter method (refractometer, Atago Ltd., g, respectively. In the females, the body weights were
Japan), and serum biochemical constituents, glutamic lower than those of the males in all strains, and were
BLOOD AND BODY WEIGHT VALUES IN SHR, SHRSP, WKY 69

lower in SHR and SHRSP than in the WKY after 8


weeks. The values (mean SD) in the SHR, SHRSP
and WKY rats at 30 weeks were 212 8 g, 196 18 g
and 262 13 g, respectively.
The systolic blood pressures in both sexes of SHR
and SHRSP rats were 180200 mmHg at 6 weeks of
age. Thereafter, the blood pressures of SHRSP elevated
to 250 mmHg at 8 weeks in males and at 17 weeks in
females, and to 300 mmHg at 18 weeks in males and at
28 weeks in females, respectively. Those of the SHR
elevated to 230250 mmHg in males after 12 weeks
and 220230 mmHg in females (Fig. 2). In contrast,
the blood pressures of the WKY were 140150 mmHg
in males and females from 630 weeks of age, though
Fig. 2. Systolic blood pressures of male and female WKY/Izm,
slightly higher in males than in females. SHR/Izm, and SHRSP/Izm rats from 630 week of age.
The hematological values are shown in Table 1. Values are mean SD.
Erythrocytes were significantly higher at 16 and 30
weeks than at 8 weeks old in the males of each strain,
and higher in SHR and SHRSP than in WKY rats at all SHRSP than the WKY at 8 and 16 weeks. Large indi-
time points. Hemoglobin and hematocrit were high at vidual variations were observed for each value in the
16 weeks of age in the SHR and SHRSP, and tended to SHRSP at 30 weeks of age.
be low at 30 weeks in each strain except for the female The values of serum biochemical constituents are
WKY. Leukocytes decreased at 16 weeks of age, then shown in Table 2. Total protein and GOT increased at
slightly increased in all strains at 30 weeks, though 16 and 30 weeks of age in all strains. The GPT did not
they were lower in the SHRSP than WKY at 8 and 16 change in any of the strains, except for high values of
weeks. Thrombocytes decreased in the WKY at 16 and male SHR and SHRSP, because of large individual
30 weeks of age, and were lower in the SHR and variations. The ALP decreased at 16 and 30 weeks in

Table 1. Hematological values and concentration of total protein in WKY, SHR and SHRSP

Strain Male Female


8 weeks 16 weeks 30 weeks 8 weeks 16 weeks 30 weeks

Erythrocyte WKY 732 28 811 14* 784 61* 718 34 732 15 705 14
(104/ml) SHR 786 15# 898 17*, # 901 12*, # 746 26 822 99 780 45*,#
SHRSP 768 26# 876 57*,# 799 123 698 33 889 30*,# 761 122
Hg WKY 15.6 0.6 15.7 0.2 15.8 0.9 15.6 0.6 14.8 0.3* 14.5 0.3*
(g/dl) SHR 15.9 0.4 16.2 0.2# 16.0 0.3 15.6 0.5 15.6 1.2 14.9 0.8*
SHRSP 15.8 0.5 16.0 0.9 14.6 1.8 14.9 0.8 16.6 0.5*,# 14.1 2.3
Ht WKY 43.2 1.6 42.9 0.7 42.2 2.2 41.3 1.8 39.7 0.8 38.2 0.7*
(%) SHR 44.6 1.1 45.4 0.8*,# 43.8 0.8# 41.0 1.6 43.2 2.3# 40.9 2.0#
SHRSP 41.4 1.5# 43.6 2.3 41.5 5.6 36.7 1.6# 44.8 1.6*, # 39.2 6.6
Leucocyte WKY 115 25 88 10* 91 16 86 9 82 14 91 7
( 102/ml) SHR 97 17 90 11 92 10# 83 12 73 15* 79 12
SHRSP 68 16# 59 8*,# 80 19* 61 15# 48 7# 90 27*
Thrombocyte WKY 95 11 83 3* 82 4* 88 4 80 4* 68 5*
(104/ml) SHR 71 15# 70 4# 63 7# 64 24# 72 9# 65 6
SHRSP 76 6# 48 11*,# 77 20 61 27# 65 4# 77 20

* Significantly different from the value at the age of 8 weeks in each strain (p<0.05). # Significantly different from the value of
WKY at the same age (p<0.05). Values are mean SD.
70 S. FUKUDA, S. TSUCHIKURA AND H. IIDA

Table 2. Concentrations of serum biochemical constituents in WKY, SHR and SHRSP

Strain male female


8 weeks 16 weeks 30 weeks 8 weeks 16 weeks 30 weeks

TP WKY 5.5 0.2 6.4 0.2* 6.4 0.3* 5.6 0.4 6.3 0.4* 6.3 0.2*
(g/dl) SHR 5.7 0.2# 6.3 0.2* 6.5 0.3* 5.5 0.2 6.0 0.1* 6.1 0.1*,#
SHRSP 5.6 0.3 6.1 0.2*,# 6.7 1.0* 5.2 0.2# 6.4 0.2* 6.4 0.8*
GOT WKY 48.7 4.8 53.8 15.6 69.8 9.4* 54.3 11.2 51.9 9.0 97.5 22.3*
(U/l) SHR 48.7 14.7 60.8 27.3 99.4 37.7* 43.7 2.3# 51.7 5.2* 47.8 9.6#
SHRSP 38.2 4.4# 49.6 15.8* 69.2 23.2* 33.8 1.6# 50.6 5.0* 63.8 17.8*,#
GPT WKY 20.6 1.1 19.5 5.5 21.7 3.5 19.1 2.7 18.7 2.3 31.6 8.6*
(U/l) SHR 29.5 10.7 30.1 9.0# 86.2 67.6*,# 20.0 0.8 21.6 4.8 26.1 3.9*
SHRSP 26.0 2.4# 29.5 21.1 45.7 33.4 22.4 1.6# 26.1 3.6*,# 28.7 9.8
ALP WKY 291 36 141 8* 152 12* 204 11 111 18* 157 13*
(U/l) SHR 252 20# 145 10* 135 19*,# 186 13# 101 16* 125 16*,#
SHRSP 229 23# 136 34* 135 34* 173 12# 120 11* 136 26*,#
BUN WKY 14.0 1.2 20.3 2.0* 17.2 1.6* 17.3 2.0 19.9 2.2* 19.7 2.3
(mg/dl) SHR 16.0 2.6# 24.7 1.4*,# 20.4 2.7*,# 12.1 0.8# 17.4 1.3* 14.7 0.9*,#
SHRSP 12.0 1.4# 16.4 2.6*,# 19.7 6.1*,# 11.8 1.7# 16.5 1.5*,# 18.5 2.9*,#
Creatinine WKY 0.419 0.019 0. 527 0.047* 0.576 0.053* 0.466 0.022 0.559 0.049* 0.585 0.02*
(mg/dl) SHR 0.409 0.039 0.465 0.041* 0. 590 0.039* 0.448 0.013 0.483 0.040*,# 0.566 0.052
SHRSP 0.426 0.039 0.469 0.052# 0.691 0.138*,# 0.453 0.045 0.547 0.056* 0.671 0.062*,#
Glucose WKY 171 9 156 10* 157 21 159 19 167 17 158 15
(mg/dl) SHR 165 14 159 8 191 14*,# 156 15 165 63 215 37*,#
SHRSP 177 16 164 17 183 31 175 18 186 14# 167 26
Total Ca WKY 10.0 0.4 9.5 0.3* 9.2 0.6* 10.3 0.3 10.0 0.5 9.6 0.3*
(mg/dl) SHR 9.8 0.6 9.5 0.4 9.0 0.4* 9.6 0.7# 9.6 0.7 9.4 0.6
SHRSP 10.3 0.5 10.3 0.3# 11.2 1.0*,# 10.0 0.4# 10.8 0.4*,# 10.5 0.8#
Phosphorus WKY 8.4 0.7 5.7 0.7* 5.6 0.8* 8.0 0.4 5.7 0.7* 6.0 1.1*
(mg/dl) SHR 8.0 0.7# 6.3 0.7* 5.9 1.1* 7.8 0.8 6.9 0.8# 6.0 0.9*
SHRSP 7.6 0.5# 5.9 0.7* 7.9 1.0# 7.1 0.6# 6.8 0.8# 6.7 1.3#
Ca+ WKY 1.28 0.04 1.24 0.03* 1.25 0.02 1.28 0.04 1.26 0.04 1.29 0.02
(U/l) SHR 1.26 0.04 1.23 0.03 1.22 0.03 1.23 0.05# 1.23 0.05 1.24 0.02#
SHRSP 1.35 0.05# 1.33 0.03# 1.42 0.06*,# 1.38 0.07# 1.32 0.03*,# 1.39 0.05#
Na+ WKY 174.3 4.8 141.5 1.5* 140.8 1.5* 169.8 3.5 141.5 1.1* 141.6 1.2*
(U/L) SHR 165.9 3.4# 143.5 1.4*,# 145.1 1.8*,# 163.7 4.2# 143.0 1.1*,# 143.5 1.5*,#
SHRSP 164.4 2.2# 142.5 1.7* 148.8 9.3*,# 162.2 4.0# 143.4 1.5*,# 143.1 1.5*
K+ WKY 5.40 0.82 4.71 0.28 4.92 0.79 5.15 0.94 4.40 0.38* 4.38 0.44
(U/L) SHR 4.88 0.26 4.56 0.37 4.40 1.18 4.77 0.98 4.86 1.22 3.98 0.37#
SHRSP 4.59 0.46# 4.31 0.42# 4.45 0.86 4.32 0.22# 4.81 1.27 3.91 0.31*
Cl WKY 97.4 1.4 99.7 0.9* 101.5 2.2* 98.1 1.1 100.3 1.6* 101.7 2.3*
(U/L) SHR 100.9 1.4# 101.3 1.3# 105.4 3.3*,# 101.6 1.5# 101.9 1.3 90.2 32.2
SHRSP 101.7 0.7# 106.2 9.7 101.6 3.6 101.7 1.3# 103.1 1.2# 100.7 4.6

* Significantly different from the value at the age of 8 weeks in each strain (p<0.05). # Significantly different from the value of WKY at
the same age (p<0.05). Values are mean SD.

all strains, but was lower in male and female SHR and at 8 weeks of age. The phosphorus decreased at 16 and
SHRSP at 8 weeks and in female SHRSP at 30 weeks. 30 weeks in all strains, except for male SHRSP at 30
The values of BUN and creatinine increased at 16 and weeks. The values of Ca2+ were higher in the SHRSP
30 weeks in all strains. The glucose values were high than in the WKY and SHR at all time points. The
at 30 weeks in male and female SHR. Total calcium values of Na + decreased at 16 and 30 weeks in all
was lower in the SHR, and higher in the SHRSP than strains, while K+ and Cl showed no particular ten-
the WKY at all time points, except for female SHRSP dency.
BLOOD AND BODY WEIGHT VALUES IN SHR, SHRSP, WKY 71

Table 3. Weights of various organs in WKY, SHR and SHRSP (values are percent as 104 of body weight at 8, 16 and 30 weeks of age)

Strain male female


8 weeks 16 weeks 30 weeks 8 weeks 16 weeks 30 weeks

Brain WKY 83.97 5.52 53.70 2.79* 44.13 7.05* 114.37 2.92 85.78 3.82* 67.75 11.14*
SHR 76.56 5.43# 56.18 2.10* 44.76 2.54* 110.67 4.68 89.91 5.67* 61.21 9.06*
SHRSP 83.84 5.25 63.67 3.99*,# 77.16 29.99# 114.88 3.73 87.12 2.06* 96.17 13.66*,#
Heart WKY 37.45 3.52 28.59 1.67* 28.77 3.45* 36.22 2.72 30.37 1.19* 31.91 2.86*
SHR 46.63 6.24# 40.30 1.92*,# 35.72 3.94*,# 50.90 4.83# 48.29 2.40# 42.41 4.47*,#
SHRSP 49.55 4.87# 45.87 3.19# 55.83 5.09*,# 51.26 4.74# 45.22 3.40# 61.59 8.35*,#
Lung WKY 43.02 1.63 32.37 5.55* 32.09 2.22* 47.91 2.12 43.46 3.93 40.53 3.74*
SHR 47.05 2.07# 41.95 6.26# 37.33 6.49 54.84 5.97# 58.05 12.89# 39.51 6.67*
SHRSP 47.78 6.54 46.24 4.93 64.65 27.47# 49.60 4.98 52.37 14.93 63.05 13.40
Thymus WKY 17.57 0.84 7.03 0.54* 6.15 0.88* 21.62 2.90 9.65 1.02* 10.43 3.44*
SHR 13.12 1.87# 4.76 1.02*,# 5.37 1.09* 15.83 3.47# 6.39 2.12*,# 7.46 2.42*
SHRSP 15.71 1.34# 4.94 1.10* 5.56 1.95* 20.46 1.69 8.10 1.06*,# 8.28 3.64*
Liver WKY 429.53 24.56 348.41 19.60* 283.58 20.23* 463.67 19.52 370.92 13.25* 358.98 21.58*
SHR 470.79 16.60# 436.35 32.14*,# 332.39 22.84*,# 476.21 22.88 385.44 18.54*,# 336.91 25.37*,#
SHRSP 446.06 33.25 416.70 16.88*,# 420.18 44.69# 427.75 32.22# 380.54 15.43* 443.40 43.05#
Kidneys WKY 41.18 2.13 32.23 2.12* 29.81 2.30* 40.80 1.88 33.68 2.67* 31.18 1.92*
SHR 44.21 2.22# 37.20 2.07*,# 32.63 1.54*,# 44.49 3.37# 37.11 2.26*,# 33.87 2.93*,#
SHRSP 44.84 1.62# 39.09 2.13*,# 44.59 4.29# 49.16 3.28# 37.19 3.84*,# 43.36 4.16*,#
Adrenal glands WKY 1.30 0.21 0.63 0.12* 0.50 0.16* 1.67 0.26 1.37 0.22* 1.34 0.48*
SHR 0.96 0.14# 0.69 0.14* 0.48 0.11* 1.81 0.37 1.26 0.22* 0.92 0.21*,#
SHRSP 1.16 0.17 0.72 0.14*,# 0.76 0.20*,# 1.46 0.23# 1.25 0.13* 1.46 0.45
Spleen WKY 17.92 0.73 12.55 0.55* 10.63 0.63* 18.06 0.61 14.07 0.79* 13.54 1.88*
SHR 15.71 0.86 14.03 0.77*,# 10.78 0.73* 16.58 1.90 15.91 2.04# 13.21 1.05*
SHRSP 16.87 1.40# 16.50 1.62# 21.04 5.12# 17.60 1.31 16.95 1.03# 29.18 9.74*
Pancreas WKY 26.44 6.10 22.83 3.96 24.90 4.94 35.72 4.93 34.17 6.68 32.36 12.44
SHR 23.56 4.53 22.70 5.38 23.89 5.45 31.95 4.73 38.06 8.74 32.67 14.33
SHRSP 23.38 4.89 26.59 10.23 29.01 13.11 30.60 4.79 31.17 11.44 46.06 15.31*,#
Testes /Ovaries WKY 73.01 2.83 54.36 3.21* 27.37 9.13* 2.17 0.55 1. 80 0.30* 1.41 0.43*
SHR 69.92 5.76 51.65 3.99*,# 31.90 2.78* 1.99 0.41 1.59 0.44*,# 1.18 0.19*,#
SHRSP 67.11 10.98 67.71 5.56# 41.71 4.78*,# 1.74 0.43# 1.39 0.33* 1.43 0.49*
Digestive tract WKY 495.00 45.96 361.40 26.18* 215.61 50.22* 580.49 42.66 405.27 19.75* 363.68 31.92*
SHR 459.41 41.00 352.84 32.77* 226.34 21.94* 546.95 19.11 402.81 51.09* 302.10 19.32*,#
SHRSP 425.35 25.69# 325.46 18.48*,# 328.91 25.95*,# 507.64 31.17# 418.78 19.94*,# 468.79 43.37*,#
Muscle WKY 3.17 0.30 2.88 0.16 3.05 0.27 3.24 0.22 3.27 0.11 3.33 0.46
(Soleus) SHR 4.00 0.12# 4.12 0.65# 4.11 0.30# 4.57 0.49# 4.13 0.44# 4.07 0.19#
SHRSP 3.33 0.24 2.86 0.26 3.25 0.44 3.19 0.19 2.64 0.45*,# 3.71 0.43*

* Significantly different from the value at the age of 8 weeks in each strain (p<0.05). # Significantly different from the value of WKY at
the same age (p<0.05). Values are mean SD.

The values for the organ weights are shown in Table SHRSP than the WKY and SHR at 30 weeks of age.
3, in which they are presented as the rate ( 104) of At autopsy, brain hemorrhage in the SHRSP was ob-
body weights to compare strains and sexes, because the served in 8 of 11 males and 10 of 12 females, and
large strain and sex differences in body weights were thereafter irregularities such as hollow portions and/or
seen at 16 and 30 weeks of age. Also, the weights of unevenness on the surface was found in all rats. Val-
bilateral adrenal glands, kidneys, and testes/ovaries were ues for the heart decreased with aging in all strains
combined because there were no significant differences except in male and female SHRSP at 30 weeks of age,
between right and left sides. The brain weights de- and at each of the measured points, those of the SHRSP
creased with aging, and were lower in males than in were significantly higher than in the other groups, fol-
females in each strain, and significantly higher in the lowed by the SHR. The values for the lung and pancreas
72 S. FUKUDA, S. TSUCHIKURA AND H. IIDA

in the SHRSP were higher at 30 weeks old than those the small intestine [24]. The values of various items
at 8 and 16 weeks, and also than the SHR and WKY at in the SHRSP at 30 weeks of age varied with large
30 weeks. Thymus values decreased with aging in all individual differences, suggesting that the alterations in
strains. Values for the liver, kidneys, adrenal glands, various organs, including the brain, might be progress-
spleen, and digestive tract decreased in all strains with ing due to prolonged hypertension. Although the
aging, and also were higher in the SHRSP than the present study was carried out to obtain fundamental
WKY and SHR at 30 weeks. Values for the testes and data for SHR, SHRSP, and WKY rats, further studies
ovaries decreased in all strains with aging. Values for such as those involving pathological examinations will
the soleus were higher in the male and female SHR at be necessary to clarify the features of these strains.
all measured points.
Regarding the clinical features of the SHRSP strain Acknowledgments
which has blood pressure elevating with aging, the hair
becomes bristly and dirty, and the temperament of the We would like to thank Mr. Xueming Yan for his
animals becomes nervous in response to stimulation help with the autopsy of rats and statistical analysis of
such as sound and restraint compared with SHR and the data.
WKY. These findings may be related to the increase in
weight of the adrenal glands. Nevertheless the body References
weight of the SHRSP continued to increase with aging,
with the increases in the values for various organs such 1. Fukuda, S., Tsuchikura, S., Iida, H., Ikeda, K., Nara, Y.,
and Yamori, Y. 1992. Genetic Hypertension. 218: 421
as the brain, heart, lung, liver, and spleen, suggesting 423.
the presence of alterations in these organs due to con- 2. Fukuda, S., Iida, H., Tsuchikura, S., Nara, Y., Ikeda, K.,
tinuous hypertension over a long period. However, the and Yamori, Y. 1994. Jpn. Heart J. 35: 532.
almost complete lack of change in the levels of serum 3. Fukuda, S., Iida, H., Tsuchikura, S., Ikeda, K., Nara, Y.,
and Yamori, Y.1995. Jpn. Heart J. 36: 508.
biochemical constituents such as GOT, GPT, and ALP
4. Fukuda, S., Tsuchikura, S., Iida, H., Ikeda, K., Nara, Y.,
indicates that the physiological functions of these or- and Yamori Y.1995. Clin. Exp. Pharmacol. Physiol. 22:
gans may stay relatively normal. However, the increases S240241.
in weight of the kidneys with elevations of BUN and 5. Tsuchikura, S., Fukuda, S., Iida, H., Ikeda, K, Nara, Y., and
Yamori, Y. 1992. Genetic Hypertemsion. 218: 417419.
creatinine may indicate the presence of functional dam-
6. Yamori, Y., Fukuda, S., Tsuchikura, S., Ikeda, K., Nara,
age and alterations. The high values of total and ionized Y., and Horie, R.1991. Clin. And Exper. Hyper.-Theory
calcium might be related to not only hypertension, but and Proctice. A13: 755762.
also osteoporosis, probably due to a release of calcium 7. Yamori, Y. 1984. Experomental and genetic models of
by parathyroid hormone against hypocalcemia caused hypertension. pp. 240255. In: deJong W. et. Handbook of
Hypertension. Elsevier, Amsteram.
by urinary high Ca excretion and low Ca absorption of