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Neurosteroid modulation of arterial baroreflex-sensitive neurons in rat rostral ventrolateral medulla.
- Source :
-
The American journal of physiology [Am J Physiol] 1998 Apr; Vol. 274 (4), pp. R903-11. - Publication Year :
- 1998
-
Abstract
- The major metabolite of progesterone, 3 alpha-OH-dihydroprogesterone (3 alpha-OH-DHP), is the most potent endogenous positive modulator of central nervous system GABAA receptors. Acute intravenous administration of 3 alpha-OH-DHP to virgin female rats potentiates arterial baroreflex sympathoinhibitory responses. The current experiments tested the possibility that circulating 3 alpha-OH-DHP potentiates central GABAergic influences in the rostral ventrolateral medulla (RVLM). The unit activity of spontaneously active, spinally projecting, and arterial pressure-sensitive neurons was recorded in the RVLM of urethan-anesthetized rats. Arterial pressure sensitivity of RVLM neurons was tested before (control) and 10 min after bolus injection (44 microliters i.v.) of 3 alpha-OH-DHP (1.12 micrograms/kg, n = 19) or vehicle (40% beta-cyclodextrin, n = 8). Both threshold pressure and saturation pressure for inhibition of RVLM neurons were decreased after acute administration of a physiological dose of 3 alpha-OH-DHP (1.12 micrograms/kg i.v.), which produces plasma concentrations similar to those seen during pregnancy (20-30 ng/ml), suggesting potentiated responsiveness to endogenously released GABA. Following suppression by 3 alpha-OH-DHP, high doses of the inactive stereoisomer 3 beta-OH-DHP (112-224 micrograms/kg i.v.; n = 8) restored unit activity, presumably by displacing 3 alpha-OH-DHP from the neurosteroid binding site on GABAA receptors.
- Subjects :
- Animals
Blood Pressure drug effects
Differential Threshold
Female
Medulla Oblongata cytology
Osmolar Concentration
Pregnanolone blood
Pregnanolone pharmacology
Rats
Rats, Sprague-Dawley
Spinal Cord physiology
Sympathetic Nervous System cytology
Sympathetic Nervous System physiology
Synaptic Transmission physiology
gamma-Aminobutyric Acid physiology
Arteries innervation
Baroreflex physiology
Medulla Oblongata physiology
Neurons physiology
Pregnanolone physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9513
- Volume :
- 274
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The American journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 9575950
- Full Text :
- https://doi.org/10.1152/ajpregu.1998.274.4.R903