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: D T Van den Berg, E R de Kloet, W de Jong
• Journal: The American journal of physiology (Am J Physiol) Vol. 267 Issue 6 Pt 1 Pg. E927-33 (Dec 1994) ISSN: 0002-9513 [Print] United States
• PMID: 7810636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mineralocorticoid Receptor Antagonists
• Receptors, Mineralocorticoid
• Spironolactone
• Desoxycorticosterone
• Sodium Chloride
• RU 28318

Topics

• Animals
• Blood Pressure (drug effects)
• Brain (drug effects)
• Desoxycorticosterone
• Heart Rate (drug effects)
• Hypertension (physiopathology)
• Male
• Mineralocorticoid Receptor Antagonists (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Mineralocorticoid (physiology)
• Sodium Chloride
• Spironolactone (analogs & derivatives, pharmacology)