Intracerebroventricular administration of a glucocorticoid receptor antagonist enhances the cardiovascular responses to brief restraint stress.
Intracerebroventricular (i.c.v.) administration of the glucocorticoid receptor antagonist 17beta-hydroxy-11beta(4-dimethylamino-phenyl)17alpha-(1-propynyl)estra-4,9dien-3one (RU38486) in conscious rats slowly increased systolic blood pressure as assessed with the indirect tail cuff method. However, direct measurement of blood pressure in freely moving rats did not reveal changes in blood pressure after i.c.v. injection of this antagonist either 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 degrees C) 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 receptor or the mineralocorticoid receptor antagonist and were either left undisturbed 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 restraint, blood pressure and heart rate showed a rapid increase. The mineralocorticoid receptor antagonist administered i.c.v. did not affect these stress-induced increases in cardiovascular responses. The glucocorticoid receptor antagonist i.c.v. significantly increased the heart rate and pressor response at 24 h. In the undisturbed rats, neither basal heart rate nor blood pressure were affected by either antagonist during the circadian cycle. In conclusion, the blockade of central glucocorticoid receptor causes a long-lasting facilitation of the stress-induced pressor and heart rate response, which does not require a 2-week training to the condition of heat and stress.
Van Acker
S A
SA
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, P.O. Box 9503, 2300 RA, Leiden, The Netherlands.
Fluttert
M F
MF
Sibug
R M
RM
De Kloet
E R
ER
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D012149:Restraint, Physical; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*; D013997:Time Factors
D011965:Receptors, Glucocorticoid; D013148:Spironolactone; D015735:Mifepristone; C041006:RU 28318