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Chronic heart failure in male Lewis rats alters corticotropin releasing hormone receptor‐2 (CRH‐R2) mRNA expression in both cardiac and brain tissue
Author(s) -
Hayward Linda F.,
Dickerson Erin E,
Yoo JeungKi,
Christou Demetra D,
Ferreira Leonardo F
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.697.14
Subject(s) - medicine , endocrinology , corticotropin releasing hormone , hypothalamus , urocortin , receptor , downregulation and upregulation , chemistry , biochemistry , gene
In heart failure (HF) circulating levels of urocortin, a positive inotrope and potent vasodilator, are elevated but peripheral actions are limited by downregulation of the endogenous receptor CRHR2. Urocortin is also readily transported into the brain where it can be anxiolytic. The present study was undertaken to test the hypothesis that chronic HF is also associated with a central downregulation of CRH‐R2 receptors and may contribute to HF‐associated mood disorders. Male Lewis rats underwent ligation of the left anterior descending coronary artery to induce HF (n=7) or a SHAM (n=6) operation and were studied 16 weeks post‐surgery. HF was characterized by a significant reduction in fractional shortening (29±2 vs 46±2 %, HF vs SHAM). CRH‐R2 mRNA levels from HF animals were found to be decreased in the right ventricle (68±13 % of SHAM) and hypothalamus (75±13% of SHAM) and slightly increased in the dorsal pons (112±5% SHAM), but unchanged in the amygdala and hippocampus. A positive relationship between cardiac CRH‐R2 receptors and hypothalamic CRH‐R2 receptor expression was also identified. Urocortin and CRH mRNA levels in the hypothalamus were found to be down‐regulated in HF (<75%) compared to SHAM. These observations suggest that autonomic and psychological changes associated with HF may be linked to a change in the balance of CRH‐R2 receptors in the hypothalamus and dorsal pons.