Mineralocorticoid antagonist inhibits stress-induced blood pressure response after repeated daily warming.
We report here that with a direct method for measurement of cardiovascular parameters in conscious rats, intracerebroventricular administration of the mineralocorticoid receptor (MR) antagonist RU-28318 (100 ng) reduces the blood pressure, heart rate, and the corticosterone response to a brief restraint stress, provided the rats were previously subjected to a daily 30-min exposure to 32 degrees C for 2 wk. The daily exposure to warming and restraint stress are applied identically to the training procedure required for indirect blood pressure measurement using the tail-cuff method. The basal arterial pressure is not affected by the MR antagonist. The effect of the MR antagonist on the stress-induced pressor response develops with a delay of several hours in the normotensive rats. The corticosterone response to daily warming and stress is also attenuated by the intracerebroventricular infusion of MR antagonist but with shorter onset and shorter duration. The findings suggest that conditioning to daily warming and stress imposes mineralocorticoid dependency of the pressor response, which involves MR functioning in brain.
Van den Berg
D T
DT
Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, The Netherlands.
de Jong
W
W
de Kloet
E R
ER
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006358:Hot Temperature; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013312:Stress, Physiological / Q000503:physiopathology*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; C041006:RU 28318; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone