Establishment of a novel strain of spontaneously hypertensive rat with a defect of ascorbic acid biosynthesis, and the effect of ascorbic acid deficiency on the hypertension

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To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, establishment of a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis was conducted. The od gene (L-gulono-γ-lactone oxidase gene) of ODS 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 190-200mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed ant ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure lower than 110mmHg. The wall to lumen ratio of testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When fed a diet supplemented with ascorbic acid (300mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. It is expected 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 deficiencv in these rats could be controlled at will both in concentration and duration.