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Blockade of Acid‐Sensing Ion Channels Attenuates the Skeletal Muscle Metaboreflex in Humans
Author(s) -
Fernandes Igor Alexandre,
Campos Monique Opuszcka,
Mansur Daniel Elias,
Mattos João Dario,
Rocha Marcos Paulo,
Rocha Natalia Galito,
Nóbrega Antonio Claudio Lucas
Publication year - 2016
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.30.1_supplement.995.2
Subject(s) - microneurography , acid sensing ion channel , medicine , myogenic contraction , blood pressure , reflex , skeletal muscle , amiloride , femoral nerve , cardiology , endocrinology , anesthesia , chemistry , heart rate , baroreflex , ion channel , sodium , organic chemistry , smooth muscle , receptor
Recent animal studies indicate that acid‐sensing ion channels (ASICs) play a role in evoking the metabolic component of the exercise pressor reflex. Nonetheless, it is still unclear whether these findings can be translated to humans. Our purpose was then to investigate the contribution of ASICs in mediating the metaboreflex‐induced increase in blood pressure and muscle sympathetic nerve activity in a human model. Five healthy subjects (32 ± 5 yrs) underwent two experimental conditions: (1) Control (C) and (2) Amiloride (AMD, 3 hours after oral administration of 5 mg of amiloride + 50 mg of hydrochlorothiazide), a non‐selective antagonist of ASICs. In each condition, beat‐by‐beat mean blood pressure (MBP, Finometer), muscle sympathetic nerve activity (MSNA, peroneal nerve microneurography) and femoral artery blood flow (FBF, Doppler ultrasound) were recorded during rest, static handgrip exercise (SHE, 2 min at 30% of the maximal voluntary contraction) and post‐exercise muscle ischemia (PEMI, 2 min). Blood samples were taken from the antecubital vein of the exercising arm during the last 30 s of PEMI and changes on lactate concentration were determined. MBP responses were slightly but significantly attenuated during SHE in the AMD condition (AMD +29.6 ± 7.0 vs. C +35.3 ± 8.4 mmHg, p = 0.05). A smaller increase in MSNA (N = 4) was also observed as a consequence of ASICs blockade (AMD +6.1 ± 3.5 vs. C +12.5 ± 4.2 bursts/min, p = 0.013). Similarly, AMD attenuated the PEMI‐induced increases in both MBP (AMD +18.9 ± 2.0 vs. C +31.35 ± 4.3 mmHg, p = 0.02) and MSNA (AMD +10.0 ± 4.3 vs. C +21.6 ± 1.4 bursts/min, p = 0.04). Increases in lactate concentration (AMD +1.00 ± 1.5 vs. C + 1.85 ± 0.15 mmol/l, p > 0.05) were similar between the experimental conditions. Femoral blood flow and conductance did not present substantial changes (p > 0.05). Although AMD antagonizes ASICs when administered in small doses, its influence on epithelial or voltage‐gated sodium channels and a related impairment in the impulse conduction in sensory nerves must not be discarded. To test the hypothesis that the attenuation of the skeletal muscle metaboreflex was only a consequence of non‐selective blockade of ASICs, MBP (N = 4) and MSNA (N = 2) responses were also recorded during rest and a cold pressor test (CPT, 20 min after PEMI). AMD had no impact on MBP (AMD +23.6 ± 3.7 vs. C +20.5 ± 4.2 mmHg; P > 0.05) and MSNA (AMD +22.9 ± 3.0 vs. C +23.6 ± 6.3 bursts/min, P > 0.05) responses during CPT, indicating that there was no impairment on sensory nerves ability to generate and conduct action potentials. Therefore, our findings suggest that ASICs also play a role in evoking the skeletal muscle metaboreflex in humans. Support or Funding Information Grant Funding Source: CNPq, FAPERJ, CAPES e FINEP