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Exercise Training (ExT) Normalizes Subfornical Organ (SFO)‐ Mediated Sympathoexcitation in Chronic Heart Failure (HF)
Author(s) -
Llewellyn Tamra L,
Zheng Hong,
Sharma Neeru M,
Patel Kaushik P
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.699.14
Subject(s) - subfornical organ , microinjection , medicine , endocrinology , losartan , angiotensin ii , renin–angiotensin system , tonic (physiology) , chemistry , receptor , blood pressure
ExT normalizes sympathoexcitation (SymEx) exhibited in HF, however the underlying mechanisms are not clear. The SFO is involved in dictating SymEx and is influenced by peptides such as angiotensin (Ang) II due to its weak blood‐brain barrier. We hypothesized that neuronal activity in the SFO would be enhanced in HF and contribute to increased Ang II‐mediated SymEx, and that ExT would reverse this process. HF induced by coronary artery ligation in Sprague‐Dawley rats was confirmed by echocardiography 4 weeks after surgery. HF rats displayed increased neuronal activity in the SFO, as assessed by FosB immunohistochemistry (101 ± 9 vs. 29 ± 2 cells). This increase was attenuated after 4 weeks of treadmill ExT (36 ± 7 cells). In anesthetized rats, microinjection of Ang II into the SFO increased renal sympathetic nerve activity (RSNA) to a greater extent in HF (23 ± 3 vs. 9 ± 1%; 100 pmol), and was normalized after ExT (8 ± 2%). ExT also abolished the decrease in RSNA in HF rats after losartan microinjection into the SFO (−21 ± 4 vs. −1 ± 3%; 200 pmol), implying higher endogenous Ang II tone in HF. ExT reversed the elevated mRNA and protein expression of AT 1 R in the SFO of rats with HF. The enhanced activation of the SFO by elevated tonic Ang II contributes to the enhanced SymEx exhibited in HF. The reduction in AT 1 receptors in the SFO by ExT may be responsible for restoring the neuronal activation in the SFO and SFO‐mediated SymEx. Supp. by NIH HL62222.