Chronic immunosuppression attenuates hypertension in Okamoto spontaneously hypertensive rats.

Abstract

Recent evidence suggests that hypertension in the Okamoto spontaneously hypertensive rat (SHR) may be the result of an autoimmune disorder. To test this hypothesis SHRs were given chronic immunosuppressive therapy (cyclophosphamide). The development of spontaneous hypertension was studied in SHRs receiving cyclophosphamide beginning at age 3 wk. The arterial pressure of the cyclophosphamide-treated SHRs was significantly lower than that of untreated control SHRs once the rats were 8 wk old, and this reduction in blood pressure was maintained for the duration of treatment. Also the effect of chronic immunosuppressive therapy on the maintenance of spontaneous hypertension was determined by beginning treatment in 16-wk-old SHRs. Arterial pressure was significantly less than that of untreated control SHRs after 2 wk of treatment. According to tail-cuff measurements, the level of hypertension in the SHRs was reduced by approximately 50% following 6 wk of immunosuppressive therapy. The mean arterial pressure was significantly reduced after 6 wk to 158 +/- 5.0 mmHg in immunosuppressed SHRs (n = 10) compared with 174 +/- 2.6 mmHg in control SHRs (n = 7). Cyclophosphamide treatment did not have a significant effect on the blood pressure of Wistar or Wistar-Kyoto rats or on the development or maintenance of deoxycorticosterone acetate hypertension. Chronic immunosuppression attenuates hypertension in the Okamoto SHR. These results support the hypothesis that spontaneous hypertension may be due in part to an autoimmune disorder.