We report herein the effects of long-term intracerebroventricular (icv) dexamethasone in normotensive rats. Dexamethasone (0.002, 0.02, 0.2, and 2.0 micrograms/day) or its vehicle (0 microgram/day, n = 8 each group) was infused icv via subcutaneous miniosmotic pumps (Alzet 2002) for 24 days in male conscious Wistar rats (weight range 190-240 g). Eighteen Wistar rats (weight range 200-230 g) received either vehicle or dexamethasone (0.2 and 2 micrograms/day) subcutaneously (sc) for 24 days. Systolic blood pressure (SBP, tail cuff) and body weight were recorded two times a week in the trained conscious rats. Dexamethasone (0.2 micrograms/day icv) exerted a progressive significant decrease in SBP over 24 days compared with both rats receiving vehicle and to pretreatment values (108 +/- 4 vs. 122 +/- 4 and 120 +/- 2 mmHg, P < 0.01). As previously reported, a significant increase in SBP was observed after 6 days in rats given 2 micrograms/day sc dexamethasone compared with both rats receiving vehicle and to pretreatment values (150 +/- 4 vs. 122 +/- 2 and 120 +/- 2 mmHg, P < 0.01 for both). Thereafter, SBP remained at plateau for the entire experiment. A similar significant decrease in body weight gain with age was observed in rats given icv or sc dexamethasone. Our data suggest that the glucocorticoid receptors exert opposite effects on blood pressure when stimulated at the brain level instead of at the peripheral vascular level.