Intracerebroventricular administration of a glucocorticoid receptor antagonist enhances the cardiovascular responses to brief restraint stress

Intracerebroventricular (i.c.v.) administration of the glucocorticoid recep tor antagonist 17 beta -hydroxy-11 beta (4-dimethylaminophenyl)17 alpha-(1- propynyl)estra-4,9dien-3one (RU38486) in conscious rats slowly increased sy stolic blood pressure as assessed with the indirect tail cuff method. Howev er, direct measurement of blood pressure in freely moving rats did not reve al changes in blood pressure after i.c.v. injection of this antagonist eith er in the light or in the dark phase. In the present study, the hypothesis is tested that aspects of the tail cuff procedure, involving heat (30 min, 32 degreesC) and brief restraint stress, are necessary conditions to detect the glucocorticoid receptor-mediated cardiovascular effect, Freely moving rats equipped with a telemetric transmitter to directly measure heart rate and blood pressure were injected i.c.v. with either the glucocorticoid rece ptor or the mineralocorticoid receptor antagonist and were either left undi sturbed for 24 h, or were subjected to the tail cuff procedure at 1.5, 6.5 and 23.5 h after injection. Then after 30-min warming and during brief rest raint, blood pressure and heart rate showed a rapid increase. The mineraloc orticoid receptor antagonist administered i.c.v. did not affect these stres s-induced increases in cardiovascular responses. The glucocorticoid recepto r antagonist i.c.v. significantly increased the heart rate and pressor resp onse at 24 h. In the undisturbed rats, neither basal heart rate nor blood p ressure were affected by either antagonist during the circadian cycle. In c onclusion, the blockade of central glucocorticoid receptor causes a long-la sting facilitation of the stress-induced pressor and heart rate response, w hich does not require a 2-week training to the condition of heat and stress . (C) 2001 Elsevier Science B.V. All rights reserved.