title: Central effects of mineralocorticoid antagonist RU-28318 on blood pressure of DOCA-salt hypertensive rats.
abstract: The role of brain mineralocorticoid receptor (MR) sites in the pathogenesis of mineralocorticoid hypertension was studied after an intracerebroventricular injection of the MR antagonist RU-28318. Male Wistar rats received subcutaneously implanted deoxycorticosterone acetate (DOCA) pellets and were maintained on 0.9% saline as drinking solution. Under these conditions hypertension developed in approximately 5 wk as assessed in conscious rats by means of the tail-cuff technique. During the development of this hypertension (after 3 wk of DOCA-salt treatment) a single intracerebroventricular injection of the specific MR antagonist RU-28318 reduced systolic blood pressure (SBP) as measured with the tail-cuff method. A decrease in SBP was observed 2-24 h after this intracerebroventricular injection, with the lowest SBP values occurring at 8 h. In these animals (3 wk after DOCA implantation) continuous direct blood pressure recording via chronic cannulation revealed, on the day of the intracerebroventricular injection of RU-28318, a slight increase in arterial pressure during the light phase, followed by a decrease during the dark phase. In the established hypertensive rats (5 wk after DOCA RU-28318 on the arterial pressure or heart rate was detectable. It is concluded that central MR blockade during the development of the DOCA-salt hypertension reduces blood pressure within 24 h assessed with 1) the indirect method at certain time points after exposure to warming and stress and 2) the direct method during the dark phase of the diurnal cycle.
authors: Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden University, The Netherlands.
authors: D T
authors: DT
authors: Van den Berg
authors: E R
authors: ER
authors: de Kloet
authors: W
authors: W
authors: de Jong
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003900:Desoxycorticosterone; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D012965:Sodium Chloride; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C041006:RU 28318