Role of the antiglucocorticoid RU 486 in the prevention of steroid-induced hypertension.

In the present study, we determined the effect of RU 486 on two experimental models of hypertension in the rat, deoxycorticosterone acetate (DOCA)-salt in nephrectomized rats and spontaneously hypertensive rats. Uni-nephrectomized saline-drinking male Sprague-Dawley rats were divided into three groups and each animal was given either 0.2 ml olive oil (control), 1 mg DOCA, or 1 mg DOCA + 10 mg RU 486 dissolved in 0.2 ml olive oil every third day for a period of three weeks. Within a week of steroid administration, there was a significant increase in the systolic blood pressure (SBP) in the DOCA-salt (157 +/- 3.8 mmHg) and DOCA + RU 486 (155 +/- 2.1 mmHg) treated rats over the control (116 +/- 2.6 mmHg) rats, which remained elevated throughout the experimental period. There was significant increase in the water intake and urine output in DOCA or DOCA + RU 486 treated rats as compared to the control untreated rats. In the experiment involving the spontaneously hypertensive rats, the rats were divided into three groups and each animal given 0.2 ml olive oil (control), 1 mg RU 486, or 5 mg RU 486 dissolved in 0.2 ml olive oil for six weeks. Instead of the expected decrease in the blood pressure, RU 486 significantly elevated blood pressure during the six weeks of drug administration. Water intake, urine output, and weights remained comparable in both groups. We conclude that RU 486 has no effect on the DOCA-salt model of hypertension but, surprisingly, elevates hypertension in the spontaneously hypertensive rats.