Fatiguing diaphragm contractions cause a time-dependent increase in muscle efferent sympathetic nerve activity recorded from the peroneal nerve (St Croix et al, J Physiol, in press). We tested the hypothesis that a metaboreflex arising from fatiguing diaphragmatic contractions can elicit an increase in resting leg vascular resistance (LVR) and a decrease in leg blood flow (QLEG). Healthy male subjects (n = 6, 25–36 yrs) performed two diaphragmfatiguing trials. Subjects inspired with their diaphragm to task failure (3–9 min) against resistance equal to 60% max inspiratory mouth pressure (PM), a prolonged duty cycle (TI/TTOT = 0.7), breathing frequency (fb) of 15/min, and tidal volume (VT) equal to twice eupnea; and 60% PM max, TI/TTOT = 0.4, fb = 20/min. In response to bilateral phrenic nerve stimulation, diaphragm force production was reduced (25–40%, P < 0.05) at the termination of both fatiguing trials. Mean arterial pressure (MAP) was determined with an automated blood pressure cuff. QLEG was measured in the femoral artery with pulsed Doppler ultrasound methods and leg vascular resistance (LVR = MAP/QLEG) was calculated. Vessel diameter was imaged and was unchanged during all trials. Compared to control conditions, the fatiguing trials increased LVR 25–80%, MAP increased 10–35 mmHg, and QLEG fell 10–30%. The time course of the effect was present by 2 min in all subjects and as early as 1 min in some subjects. During recovery, the observed changes were quickly dissipated (< 30 sec). QLEG and LVR were unchanged during (i) 3-min trials replicating the breathing pattern used in the fatiguing trials with no inspiratory resistance, (ii) 3-min non-fatiguing hyperoxic trials of increased central motor output (PM = 95% max, TI/TTOT = 0.35, fb = 12/min; and PM = 2% max, TI/TTOT = 0.4, fb = 45/min), and (iii) three non-fatiguing trials where inspiratory effort was gradually increased (30, 40, 50% PM max) and breathing pattern (TI/TTOT = 0.4, fb = 20/min) was constant. In summary, voluntary alterations to inspiratory effort, in the absence of fatigue, had no effect on LVR and QLEG whereas the two fatiguing trials elicited increases in LVR and decreases in QLEG. We attribute these changes to a metaboreflex originating in the diaphragm, which reaches its threshold for activation during fatiguing contractions. Supported by NHLBI
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