Centrally regulated blood pressure response to vasoactive peptides is modulated by corticosterone.
To investigate the role of brain glucocorticoid (GR) and mineralocorticoid receptors (MR) in centrally evoked blood pressure responses, the effects of intracerebroventricular (i.c.v.) administration of angiotensin II and vasopressin were studied in adrenalectomized rats with and without corticosterone or aldosterone replacement. Five groups were examined: (i) Adrenalectomy (ADX); (ii) ADX + a subcutaneously implanted 20-mg corticosterone pellet (low corticosterone); (iii) ADX + 100 mg corticosterone pellet (high corticosterone); (iv) ADX + 6 microg/24 h aldosterone via Alzet minipump (Aldo); and (v) Sham adrenalectomy (Sham). Pressor responses to 150 ng angiotensin II and 50 ng vasopressin i.c.v. were determined in freely moving rats using biotelemetry. The results show that, compared to sham rats, ADX rats showed significantly reduced pressor responses. This reduction of the pressor response to angiotensin II could be reversed and even further enhanced by replacement of the ADX rats with high corticosterone concentrations. In contrast, with aldosterone, a depressor type response was observed. Corticosterone replacement could not restore the pressor response to vasopressin. We conclude that the pressor response to centrally administered vasoactive substances is substantially attenuated by removal of the adrenals and that, in the case of angiotensin II, this is due to the lack of high concentrations of circulating corticosterone occupying both MR and GR. However, predominant MR occupancy appears to play an opposite role and attenuates the angiotensin II-induced pressor response.
van Acker
S A B E
SA
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, The Netherlands.
Oitzl
M S
MS
Fluttert
M F J
MF
de Kloet
E R
ER
D000315:Adrenalectomy; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood / Q000502:physiology*; D004327:Drinking Behavior / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D014667:Vasopressins; D000804:Angiotensin II; D003345:Corticosterone