A newly established strain of spontaneously hypertensive rat with a defectof 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 o d gene (L-gulono-gamma -lactone oxidase gene) of the ODS (Osteogenic Disord er Shionogi) rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR), and a novel con genic strain, SHR-od, was established. SHR-od showed scurvy when fed an asc orbic acid-free diet. Systolic blood pressure of male SHR-od began to incre ase at 9 weeks of age and reached 190-200 mmHg at 20 weeks of age. In 25-we ek-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 f ed a diet supplemented with ascorbic acid (300 mg/kg), ascorbic acid concen tration in SHR-od was lower in the serum and liver than that in ODS rats. T hese results indicate that ascorbic acid could be closely related to the de velopment of hypertension in SHR-od. We believe that SHR-od will be a usefu l model for experimental studies on hypertension and its complications, sin ce all of them suffer from hypertension spontaneously and the level of asco rbic acid deficiency in these rats could be controlled at will both in conc entration and duration. (C) 2001 Elsevier Science Inc. All rights reserved.