Journal article
11β-hydroxysteroid dehydrogenase Type 2 activity in hypothalamic paraventricular nucleus modulates sympathetic excitation
Hypertension (Dallas, Tex. 1979), Vol.48(1), pp.127-133
07/2006
DOI: 10.1161/01.HYP.0000224296.96235.dd
PMID: 16717146
Abstract
Aldosterone stimulates the sympathetic nervous system by binding to a select population of brain mineralocorticoid receptors (MR). These MR have an equal affinity for corticosterone that is present in substantially higher concentrations, but are held in reserve for aldosterone by activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which converts corticosterone to an inactive metabolite. Thus, colocalization of MR and 11β-HSD-2 activity may help identify brain regions that mediate the effects of aldosterone. The present studies tested the hypothesis that 11β-HSD-2 activity regulates MR-mediated responses in the paraventricular nucleus (PVN) of the hypothalamus, a forebrain region implicated in sympathetic regulation. Real-time–polymerase chain reaction revealed the presence of 11β-HSD-2 mRNA in PVN. In anesthetized adult male Sprague-Dawley rats, microinjection of the 11β-HSD-2 inhibitor carbenoxolone (CBX) into PVN increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. Intracerebroventricular injections of CBX excited PVN neurons and increased mean arterial pressure, heart rate, and renal sympathetic nerve activity. The ability of CBX to increase sympathetic activity by inhibiting 11β-HSD-2, thereby permitting corticosterone to activate MR, was confirmed by the following: Intracerebroventricular glycyrrhizic acid, another 11β-HSD-2 inhibitor, mimicked the sympathoexcitatory effects of CBX; the sympathoexcitatory effects of CBX were blocked by spironolactone, a MR antagonist. Neither CBX nor glycyrrhizic acid elicited a response in adrenalectomized rats. These findings suggest that MR in PVN contribute to sympathetic regulation and may be activated by aldosterone or corticosterone (or cortisol in humans) depending on the state of 11β-HSD-2 activity.
Details
- Title: Subtitle
- 11β-hydroxysteroid dehydrogenase Type 2 activity in hypothalamic paraventricular nucleus modulates sympathetic excitation
- Creators
- Zhi-Hua ZHANG - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesYu-Ming KANG - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesYang Yu - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesShun-Guang WEI - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesThomas J SCHMIDT - Department of Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesAlan Kim JOHNSON - Department of Psychology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United StatesRobert B FELDER - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.48(1), pp.127-133
- DOI
- 10.1161/01.HYP.0000224296.96235.dd
- PMID
- 16717146
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Publisher
- Lippincott; Philadelphia, PA; Hagerstown, MD
- Language
- English
- Date published
- 07/2006
- Academic Unit
- Molecular Physiology and Biophysics; Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984065399502771
Metrics
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