Biochemical and morphological characterization of spontaneously hypertensive hyperlipidaemic rats.
1. To develop and characterize a new animal model of hypertension and hyperlipidaemia, we cross-bred spontaneously hypertensive rats (SHR) with spontaneously hyperlipidaemic rats (HLR). 2. A new strain of spontaneously hypertensive hyperlipidaemic rats (SHHR) was established at generation 10 through selective mating of brothers and sisters (systolic blood pressure > 150 mmHg, plasma cholesterol > 150 mg/dL). Cross-bred Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats (SDWKY rats) were used as a control. 3. Adrenaline and noradrenaline levels in the plasma and adrenal medulla of male SHHR were significantly higher than those of male SDWKY rats. The tyrosine hydroxylase activity in the adrenal medulla of male SHHR was significantly higher than that of male SDWKY rats. Low-density lipoprotein expression was found in the plasma of male and female SHHR and HLR. Cholesterol 7alpha-hydroxylase mRNA expression in the liver of male SHHR was lower than that of male SDWKY rats. Endothelium lesions and lipid deposition under the endothelium were observed in the aorta of 24-month-old SHHR, especially female SHHR, but not in age-matched HLR and SDWKY rats. 4. The hypertension of this new animal model of hypertension and hyperlipidaemia may be related to increased catecholamine activity and the hyperlipidaemia may be related to changes in the expression of cholesterol 7alpha-hydroxylase mRNA and lipoprotein profiles. The SHHR may be valuable in the study of mechanisms of atherosclerosis and the evaluation of anti-atherosclerosis drugs as a new strain of cardiovascular disease.
Kumai
Toshio
T
Departments of Pharmacology, St Marianna University School of Medicine, Kawasaki, Japan. yakuri@marianna-u.ac.jp
Oonuma
Shigeko
S
Kitaoka
Yasushi
Y
Tadokoro
Mamoru
M
Kobayashi
Shinichi
S
D000818:Animals; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D004837:Epinephrine / Q000097:blood; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010375:Pedigree; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D008074:Lipoproteins; D012333:RNA, Messenger; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine