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Purpose: To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age-and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women). Results: Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups. Conclusions: Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents' stimulation and sensitivity.

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Patients with moderate‐to‐severe chronic obstructive pulmonary disease (COPD) show decrease of intercostal (IC) and increase of vastus lateralis (VL) microvascular blood flow from resting to cycling exercise. One of the mechanisms which could mediate such decrease of IC microvascular blood flow is greater sympathetically mediated vasoconstriction in the IC. Therefore, we sought to investigate the effect of a sympathoexcitatory maneuver on IC and VL microvascular blood flow and conductance at rest and during exercise. Ten patients with moderate‐to‐severe COPD (mean ± SEM: 63 ± 4 years) and eight risk, age and sex matched controls (CON; 63 ± 3 years) were assessed at seated rest and during submaximal cycling exercise at 50% peak workload. One of the hands was immersed into iced water [i.e., cold pressor test (CPT)] during the last 2 min of each condition to provoke systemic sympathoexcitation. A dye (indocyanine green) was infused in a peripheral vein before and during the CPT. Dye concentration was measured in the IC and VL muscles via near‐infrared spectroscopy (NIRS), plotted as a function of time and analyzed by linear regression. The ensuing slope was considered as the blood flow index (BFI). Vascular conductance was estimated by division of BFI by mean arterial pressure (MAP). Perceived pain was assessed by Borg’s scale. Pulmonary ventilation was measured by a pneumotachometer. The COPD group had higher resting BFI in the IC versus the CON group. In addition, resting BFI was greater in the IC than in the VL in both groups. At rest, CPT decreased BFI of IC and VL in the COPD group (IC: before CPT = 13±2 vs. during CPT = 10±1 mol/s; VL: before CPT = 5±1 vs. during CPT = 4±1 mol/s; time main effect: P = 0.01), but CPT did not change BFI of both muscles in the CON group (time main effect: P = 0.32). BFI decreased in the IC and increased in the VL from rest to exercise. During exercise, CPT did not change BFI of IC both in COPD and CON. However, CPT decreased BFI of VL during exercise in both groups (COPD: before CPT = 14±6 vs. during CPT = 10±3 mol/s; CON: before CPT = 17±7 vs. during CPT = 10±4 mol/s; time main effect: P = 0.01). CPT increased MAP at rest and exercise similarly in both groups. As a result, the CPT effect on vascular conductance was similar to the one reported for BFI in both groups. Perceived pain tended to be lower in COPD versus CON at rest, but it was similar between groups during exercise. At last, CPT did not change pulmonary ventilation at rest and during exercise. In conclusion, IC and VL of patients with COPD are similarly vulnerable to sympathetically‐induced vasoconstriction at rest. In contrast, exercise abolished the sympathetically‐induced vasoconstriction in the IC, but not in the VL in patients with COPD. Our results therefore suggest that sympathoexcitation does not seem to explain the reduction of IC microvascular blood flow during cycling exercise in COPD. Support or Funding Information Supporting or Funding Information FAPESP: 2018/03501‐4; 2017/07771‐3. CNPq; CAPES.