Evidence for a physiological role of pulmonary arterial baroreceptors in sympathetic neural activation in healthy humans

Abstract

Key points In an anaesthetised animal model, independent stimulation of baroreceptors in the pulmonary artery elicits reflex sympathoexcitation. In humans, pulmonary arterial pressure is positively related to basal muscle sympathetic nerve activity (MSNA) under conditions where elevated pulmonary pressure is evident (e.g. high altitude); however, a causal link is not established. Using a novel experimental approach, we demonstrate that reducing pulmonary arterial pressure lowers basal MSNA in healthy humans. This response is distinct from the negative feedback reflex mediated by aortic and carotid sinus baroreceptors when systemic arterial pressure is lowered. Afferent input from pulmonary arterial baroreceptors may contribute to sympathetic neural activation in healthy lowland natives exposed to high altitude. Abstract In animal models, distension of baroreceptors located in the pulmonary artery induces a reflex increase in sympathetic outflow; however, this has not been examined in humans. Therefore, we investigated whether reductions in pulmonary arterial pressure influenced sympathetic outflow and baroreflex control of muscle sympathetic nerve activity (MSNA). Healthy lowlanders (n = 13; 5 females) were studied 4–8 days following arrival at high altitude (4383 m; Cerro de Pasco, Peru), a setting that increases both pulmonary arterial pressure and sympathetic outflow. MSNA (microneurography) and blood pressure (BP; photoplethysmography) were measured continuously during ambient air breathing (Amb) and a 6 min inhalation of the vasodilator nitric oxide (iNO; 40 ppm in 21% O2), to selectively lower pulmonary arterial pressure. A modified Oxford test was performed under both conditions. Pulmonary artery systolic pressure (PASP) was determined using Doppler echocardiography. iNO reduced PASP (24 ± 3 vs. 32 ± 5 mmHg; P < 0.001) compared to Amb, with a similar reduction in MSNA total activity (1369 ± 576 to 994 ± 474 a.u min−1; P = 0.01). iNO also reduced the MSNA operating point (burst incidence; 39 ± 16 to 33 ± 17 bursts·100 Hb−1; P = 0.01) and diastolic operating pressure (82 ± 8 to 80 ± 8 mmHg; P < 0.001) compared to Amb, without changing heart rate (P = 0.6) or vascular–sympathetic baroreflex gain (P = 0.85). In conclusion, unloading of pulmonary arterial baroreceptors reduced basal sympathetic outflow to the skeletal muscle vasculature and reset vascular–sympathetic baroreflex control of MSNA downward and leftward in healthy humans at high altitude. These data suggest the existence of a lesser‐known reflex input involved in sympathetic activation in humans.

Global REACH 2018: Andean highlanders, chronic mountain sickness and the integrative regulation of resting blood pressure

“…Therefore, other factors may predispose individuals with CMS to cardiovascular disease. However, we cannot exclude the possibility that elevated sympathetic vasomotor outflow and/or arterial baroreflex dysfunction may develop in more severe CMS, with elevated pulmonary arterial pressure (Simpson et al, 2020), which may contribute to the greater cardiovascular disease risk reported in moderate and severe CMS.…”

A sympathetic view of blood pressure control at high altitude: new insights from microneurographic studies

“…Furthermore, in normoxic anesthetised animals, isolated increases in PAP elicit increases in sympathetic outflow in a positive feedback manner, via stimulation of baroreceptors located in the extra pulmonary arteries (Moore et al., 2011). The potential sympathoexcitatory role of pulmonary arterial baroreceptors in humans at HA has since been investigated (Simpson et al., 2020). During inhalation of vasodilator nitric oxide, which selectively lowered PAP by 25%, a similar reduction in MSNA burst frequency was observed in lowlanders at 4383 m (exposure range 4–9 days).…”

What happens in vagus, no longer stays in vagus

“…One hypothesis for these findings was the parallel stimulation of cardiopulmonary afferents that can elicit opposing effects on peripheral sympathetic outflow. Other work has postulated the existence of a positive feedback sympathetic reflex originating from pulmonary baroreceptors (Simpson et al 2020). To date, human work has relied on assessing reflex responses to a variety of cardiopulmonary stimuli with limited capacity to quantify afferent activity.…”

“…Other work has postulated the existence of a positive feedback sympathetic reflex originating from pulmonary baroreceptors (Simpson et al . 2020). To date, human work has relied on assessing reflex responses to a variety of cardiopulmonary stimuli with limited capacity to quantify afferent activity.…”