Pulmonary arterial mechanoreceptors modulate exercise-induced sympathetic activation in healthy humans during moderate-intensity hypoxic exercise.

Abstract

Central command, muscle afferent feedback and arterial baroreceptors all contribute to sympathetic vasoconstrictor activity during moderate-intensity dynamic exercise in humans; however, whether a causal link exists between pulmonary arterial mechanoreceptors and sympathetic outflow directed to inactive skeletal muscle (muscle sympathetic nerve activity, MSNA) remains to be explored. Twelve participants (28 ± 7 years, 2 females) performed two 6 min exercise bouts (heart rate ∼ 120∙beats∙min^-1) in hypoxia (FiO_2 = 12.5%) to elevate pulmonary artery pressure (PAP) above normal, whilst MSNA (microneurography), systemic blood pressure (photoplethysmography, BP), oxygen saturation (SpO₂) and minute ventilation (V_E) were measured continuously. Systolic PAP was estimated using Doppler echocardiography. In one trial nitric oxide was added to the inhaled air (iNO, 40 parts per million) to selectively dilate the pulmonary vasculature and reduce exercise PAP. MSNA burst frequency was supressed (30 ± 9 vs. 34 ± 9 bursts∙min^-1; p = 0.03) when exercise systolic PAP was lowered (36.8 vs. 42.9 ± 8 mmHg; p = 0.02). MSNA burst incidence (index of sympathetic baroreflex operating point) was reduced (25 ± 8 vs. 28 ± 9 bursts∙100 heartbeats^-1; p = 0.03) without any change in corresponding diastolic BP or spontaneous baroreflex gain. Mean BP, SpO₂ and V_E did not differ between trials. Together these data support a mechanistic link between pulmonary arterial mechanoreceptor activation and neurocirculatory control during hypoxic exercise. The effect of pulmonary arterial mechanoreceptor activity on exercise-induced sympathetic activation and baroreflex resetting may have consequences for sympathetic vasomotor outflow (dys)regulation in health and disease where PAP is elevated. KEY POINTS: Pulmonary arterial pressure increases proportionally to cardiac output during dynamic exercise; this pressure rise may contribute to excitation of sympathetic vasoconstrictor activity directed to skeletal muscle (muscle sympathetic nerve activity, MSNA) via stimulation of pulmonary arterial mechanoreceptors. In this study addition of nitric oxide to hypoxic inspired air (FiO₂ = 12.5%) reduced pulmonary arterial pressure during sub-maximal cycling exercise; this coincided with reduced MSNA burst frequency (vasoconstrictor outflow) and burst incidence (operating point for baroreflex control of vasoconstrictor outflow). These findings demonstrate that a signal from pulmonary arterial mechanoreceptors is involved in sympathoexcitation during hypoxic exercise. Furthermore this mechanism could be relevant clinically in pulmonary and cardiac diseases associated with pulmonary hypertension and exaggerated sympathoexcitation during exercise.