Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients

Arterial baroreflex control of muscle sympathetic nerve activity (ABRMSNA) is impaired in chronic systolic heart failure (CHF). the purpose of the study was to test the hypothesis that exercise training would improve the gain and reduce the time delay of ABRMSNA in CHF patients. Twenty-six CHF patients, New York Heart Association Functional Class II-III, EF <= 40%, peak (V) over dot O-2 <= 20 ml.kg(-1).min(-1) were divided into two groups: untrained (UT, n = 13, 57 +/- 3 years) and exercise trained (ET, n = 13, 49 +/- 3 years). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique. Arterial pressure was measured on a beat-to-beat basis. Time series of MSNA and systolic arterial pressure were analyzed by autoregressive spectral analysis. the gain and time delay of ABRMSNA was obtained by bivariate autoregressive analysis. Exercise training was performed on a cycle ergometer at moderate intensity, three 60-min sessions per week for 16 wk. Baseline MSNA, gain and time delay of ABRMSNA, and low frequency of MSNA (LFMSNA) to high-frequency ratio (HFMSNA) (LFMSNA/HFMSNA) were similar between groups. ET significantly decreased MSNA. MSNA was unchanged in the UT patients. the gain and time delay of ABRMSNA were unchanged in the ET patients. in contrast, the gain of ABRMSNA was significantly reduced [3.5 +/- 0.7 vs. 1.8 +/- 0.2, arbitrary units (au)/mmHg, P = 0.04] and the time delay of ABRMSNA was significantly increased (4.6 +/- 0.8 vs. 7.9 +/- 1.0 s, P = 0.05) in the UT patients. LFMSNA-to-HFMSNA ratio tended to be lower in the ET patients (P < 0.08). Exercise training prevents the deterioration of ABRMSNA in CHF patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao ZerbiniCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Heart, Lung, and Blood InstituteUniv São Paulo, Sch Med, Heart Inst InCor, São Paulo, BrazilUniv São Paulo, Sch Phys Educ & Sport, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilUniv Calif Los Angeles, David Geffen Sch Med, Dept Med Cardiol & Physiol, Los Angeles, CA 90095 USAUniversidade Federal de São Paulo, Dept Med, Div Cardiol, São Paulo, BrazilFAPESP: 2010/50048-1FAPESP: 140643/2009-5FAPESP: 2013/07651-7CNPq: 142366/2009-9CNPq: 301867/2010-0CNPq: 308068/2011-4FAPESP: 2013/15651-7National Heart, Lung, and Blood Institute: RO1-HL084525Web of Scienc

Molecular basis for the improvement in muscle metaboreflex and mechanoreflex control in exercise-trained humans with chronic heart failure

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 with ejection fractions <40% were randomized to untrained (n = 17; 54 +/- 2 yr) or exercise-trained (n = 17; 56 +/- 2 yr) groups. MSNA was recorded by microneurography. Mechanoreceptors were activated by passive exercise and metaboreceptors by postexercise circulatory arrest (PECA). COX-2 pathway, TRPV1, and CB1 receptors were measured in muscle biopsies. Following ET, resting MSNA was decreased compared with 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-E-2 receptor-4, and thromboxane-A(2) receptor and by decreased in muscle inflammation, as indicated by increased miRNA-146 levels and the stable NF-kappa B/I kappa B-alpha 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