2014 Oct 10. pii: ajpheart.00136.2014. [Epub ahead of print]
Molecular Basis for the Improvement in Muscle Metaboreflex and Mechanoreflex Control in Exercise-Trained Humans with Chronic Heart Failure.
Antunes-Correa LM1, Nobre TS2, Groehs RV3, Alves MJ1, Fernandes T4, Couto GK5, Rondon MU6, de Oliveira PA3, Lima M3, Mathias W Jr3, Brum PC7, Mady C, Almeida DR, Rossoni LV8, Oliveira EM9, Middlekauff HR10, Negrao CE11.
Abstract
Previous studies have demonstrated that muscle mechanoreflex and metaboreflex controls are altered in heart failure(HF), which seems to be due to changes in cyclooxygenase(COX) pathway, and changes in receptors on afferent neurons, including transient receptor potential vanilloid type-1(TRPV1) and cannabinoid receptor type-1(CB1). The purpose of the present study was to test the hypotheses: 1) Exercise training(ET) alters the muscle metaboreflex and mechanoreflex control of muscle sympathetic nerve activity(MSNA) in HF patients. 2) The alteration in metaboreflex control is accompanied by increased expression of TRPV1 and CB1 receptors in skeletal muscle. 3) The alteration in mechanoreflex control is accompanied by COX-2 pathway in skeletal muscle. Thirty-four consecutive HF patients, ejection fraction<40% were randomized to untrained (n=17, 54±2years) or exercise-trained (n=17, 56±2years) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by post-exercise circulatory arrest(PECA). COX-2 pathway, TRPV1 and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared to untrained group. During PECA (metaboreflex), MSNA responses were increased, which was accompanied by the expression of TRPV1 and CB1 receptors. During passive exercise (mechanoreflex) MSNA responses were decreased, which was accompanied by decreased expression of COX-2, prostaglandin-E2 receptor-4 and thromboxane-A2 receptor, and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-κB/IκB-α ratio. In conclusion, ET alters muscle metaboreflex and mechanoreflex control of MSNA in HF patients. This alteration with ET is accompanied by alteration in TRPV1 and CB1 expression, and COX-2 pathway and inflammation in skeletal muscle.
Copyright © 2014, American Journal of Physiology – Heart and Circulatory Physiology.
Copyright © 2014, American Journal of Physiology – Heart and Circulatory Physiology.
KEYWORDS:
Heart failure; exercise training; mechanoreflex; metaboreflex; muscle sympathetic nervous system
- PMID:
- 25305179
- [PubMed – as supplied by publisher]
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