A newly established strain of spontaneously hypertensive rat with a defect of ascorbic acid biosynthesis.
To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, we established a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis. The od gene (L-gulono-gamma-lactone oxidase gene) of the ODS (Osteogenic Disorder Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed an ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure to lower than 110 mmHg. The wall to lumen ratio of the testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When rats were fed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than that in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. We believe that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiency in these rats could be controlled at will both in concentration and duration.
Horio
F
F
Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Japan. horiof@agr.nagoya-u.ac.jp
Hayashi
K
K
Mishima
T
T
Takemori
K
K
Oshima
I
I
Makino
S
S
Kakinuma
A
A
Ito
H
H
D000375:Aging / Q000502:physiology; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D020296:Animals, Congenic; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology; D001206:Ascorbic Acid Deficiency / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004837:Epinephrine / Q000097:blood; D006579:Heterozygote; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D050544:L-Gulonolactone Oxidase; D008099:Liver / Q000201:enzymology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011922:Rats, Mutant Strains; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics; D013737:Testis / Q000098:blood supply / Q000473:pathology
D013401:Sugar Alcohol Dehydrogenases; D050544:L-Gulonolactone Oxidase; D000469:Alkaline Phosphatase; D001205:Ascorbic Acid; D009638:Norepinephrine; D004837:Epinephrine