Blood pressure changes associated with hyperinsulinemia or long-standing diabetes mellitus in spontaneously hypertensive rats

We studied the long-term change in blood pressures of spontaneously hypertensive rats (SHR) treated neonatally with streptozotocin (STZ). Two-day-old male SHR were injected intraperitoneally with 37.5–75.0 mg/kg STZ or with vehicle as control. STZ-treated SHR were divided into mildly or severely diabetic groups according to the nonfasting plasma glucose level at age 12 weeks (the former <300 mg/dl, the latter ≧300 mg/dl). In the mildly diabetic group (MD) (n = 5), body weight increased and nonfasting plasma glucose was normalized. At 52 weeks of age, fasting plasma glucose levels were lower than controls owing to hyperinsulinemia, and insulinomas were found in 60% of rats. The systolic blood pressure (SPB) as measured by a tail-cuff method, decreased after 40 weeks, and the mean BP from 44 to 52 weeks (188 ± 4 mmHg) was significantly lower than that in the control group (209 ± 3 mmHg, p < 0.01). In the severely diabetic group (SD) (n = 6), hyperglycemia persisted until 52 weeks, although its severity became less marked. BP in the SD group increased after 36 weeks, and the mean BP from 44 weeks to 52 weeks (224 ± 5 mmHg) was significantly higher than control (p < 0.05). The present study demonstrated that hypertension was ameliorated in SHR associated with hyperinsulinemia, and deteriorated with long-standing diabetes mellitus.