EFFECTS OF THE GLUCOCORTICOID ANTAGONIST RU486 IN SPONTANEOUSLY HYPERTENSIVE AND SPRAGUE-DAWLEY RATS

The effect of a low dose of the glucocorticoid receptor antagonist, RU 486, was tested in spontaneously hypertensive (SHR) and in Sprague Daw ley (SD) rats. In SD rats, RU486 (50 mu g/day, 18 days) significantly increased growth rate and thymus weight, probably by antagonising the actions of endogenous glucocorticoid hormones. Blood pressure and plas ma corticosterone levels were not affected by RU486 at this dose. In l eucocytes, RU486 treatment in vivo reduced the number of glucocorticoi d binding sites but did not affect binding affinity. In contrast, grow th rate and thymus weight were not altered in SHR when treated with th e same dose of RU486 for a longer period (60 days). Blood pressure was unaffected as were leucocyte glucocorticoid receptor characteristic. Glucocorticoid receptor binding characteristics for RU486 were similar for liver cytosol of SD and SHR. We conclude that the apparent differ ence in sensitivity to RU486 between strains is probably not due to di fferences in interaction of the antagonist with the glucocorticoid rec eptor but may be caused by differences in pharmacokinetics of RU486 be tween strains.