Development of a Strain of Spontaneously Hypertensive Rats

A male rat with spontaneously high systolic blood pressures of 150 to 175 mmHg persisting for more than one month and a female rat with blood pressures slighty above the average, 130 to 140 mmHg, were selected from among 68 Wistar strain rats in normal condition and mated to obtain F1 rats. Of these F1 rats, males and females with hypertension (blood pressure exceeding 150 mmHg) persisting for more than a month (mostly over 2 months) were mated to produce F2 rats. The procedure was repeated to obtain F3, F4, F5 and F6 rats totaliag 380 animals. The weights and blood pressures (by the tail-water-plethysmographic method) were measured once weekly biginning at 4 weeks of age, and the results can be summarized as follows : 1. In body weight, the F rats showed little difference from the normal controls. 2. The blood pressures of F rats rose with age and from generation to generation, increasing significantly above those of normotensive controls of the same age after 20 weeks of age among female F1, after 15 weeks among male F1 and also male and female F2, and after 10 weeks among all F3 to F6 rats. E. g., the average systolic blood pressure of F5 at 25 weeks of age was 206+__-18.5 mmHg in the male and 193+__-20.5 mmHg in female rats. The blood pressures of normotensive controls remained at 131 to 136 mmHg in the male and 130 to 135 mmHg in female rats after 10 weeks of age. 3. Many F rats showed spontaneous hypertension. The incidence of the spontaneous occurrence of hypertension increased, and the development of hypertension occurred at younger ages from generation to generation. All of the F3 to F6, rats developed spontaneous hypertension within 15 weeks of age. Severe hypertension with blood pressures exceeding 200 mmHg began to observed among F2. The incidence of such severe hypertension increased with each generation, so that among male animals it inceased from only 9% in F2 to 35% in F3, 42% in F4, and 56% in F5, and in female animals from 3% in F2, 16% in F3, 33% in F4, and 37% in F5. The authors have named this Wistar strain of rats with spontaneous occurrence of hypertension as "spontaneously hypertensive rats (Okamoto-Aoki)". 4. The blood pressures of β-line rats from parents with very high blood pressures were significantly higher than among α-line rats from parents with moderately high blood pressures at the same age. 5. There was no difference in the blood pressures of offsprings resulting from inbreeding and those from cross breeding. The male blood pressure averaged about 10.6 mmHg above the female value in spontaneous hypertension, and hypertension developed at lower ages in the male. 6. It is a question for future study whether the spontaneous hypertension induced in rats in this Study is comparable in characteristics with essential hypertension in man.