Abstract
Aldosterone Upregulates the Brain Renin‐Angiotensin System in Rats with Heart Failure
The FASEB journal, Vol.21(6), pp.A1266-A1266
2007
DOI: 10.1096/fasebj.21.6.A1266-b
Abstract
Activation of the brain renin‐angiotensin system (RAS) contributes to increased sympathetic drive in heart failure (HF). Plasma aldosterone (ALDO), a downstream product of the systemic RAS, crosses the blood‐brain barrier. In peripheral tissues, ALDO enhances the action of the RAS. We hypothesized that ALDO increases in the brain of HF rats and upregulates brain RAS activity. Sprague Dawley rats underwent coronary ligation to induce HF or sham surgery (SHAM). Compared with SHAM (n=5), HF (n=5) rats had high (∗P<0.05, HF vs SHAM) ALDO levels (by ELISA) in plasma (288±32∗ vs 188±25 pg/ml) and in hypothalamus (240±21∗ vs 165±19 pg/g tissue) but not in cortex. Some HF rats were treated for 4 weeks with intracerebroventricular (ICV) RU28318 (1 μg/hr, n=9), a selective mineralocorticoid receptor antagonist, or vehicle (VEH, n=10). Compared with untreated SHAM (n=9), HF+VEH rats had increased (¥P<0.05) mRNA expression for angiotensin converting enzyme (ACE, 0.031±0.003¥ vs 0.013±0.002) and angiotensin type 1 receptor (AT1‐R, 0.021±0.002¥ vs 0.009±0.001) in hypothalamus by real‐time PCR (normalized by GAPDH), and more excited (Fra‐LI positive) neurons (65±5¥ vs 29±6) in paraventricular nucleus (PVN) of hypothalamus by immunohistochemistry. Compared with HF+VEH rats, HF+RU28318 rats had less (#P<0.05) hypothalamic ACE (−29%#) and AT1R mRNA (−34%#) and fewer Fra‐LI positive neurons (−27%#) in the PVN. No effects on these variables were found in brain cortex. RU28318 had no effect on plasma ALDO. Together, these two sets of data suggest that an increase in hypothalamic ALDO in HF upregulates brain RAS activity, likely contributing to augmented sympathetic drive.
Supported by NIH HL‐063915.
Details
- Title: Subtitle
- Aldosterone Upregulates the Brain Renin‐Angiotensin System in Rats with Heart Failure
- Creators
- Yang Yu - University of IowaShun‐Guang Wei - University of IowaZhi‐Hua Zhang - University of IowaElise P Gomez‐Sanchez - University of MississippiRobert M Weiss - University of Iowa and VA Medical CenterRobert B Felder - University of Iowa and VA Medical Center
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1266-A1266
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1266-b
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Grant note
- NIH (HL‐063915)
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Internal Medicine; Cardiovascular Medicine
- Record Identifier
- 9984071633902771
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