TY - JOUR

T1 - Selective Reductions in Pulmonary Artery Pressure Lowers Sympathetic Neural Activity in Healthy Humans at High Altitude

AU - Simpson, Lydia

AU - Steele, Andrew

AU - Meah, Victoria L.

AU - Thapamagar, Suman

AU - Gasho, Christopher

AU - Drane, Aimee

AU - Oliver, Samuel

AU - Tymko, Michael M.

AU - Ainslie, Philip N.

AU - Steinbeck, Craig D.

AU - Stembridge, Mike

AU - Moore, Jonathan

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Chronically elevated sympathetic neural activity is a characteristic of many disease states. Tonic chemoreflex activation has been implicated in the development of sympathetic overactivity; however, other reflexes may also contribute. For example, in an animal model, stimulation of pulmonary baroreceptors induces a reflex increase in sympathetic neural activity. In humans, pulmonary pressure has been shown to be related to basal sympathetic activity in pulmonary hypertension; however a critical step in determining a causal link is to establish whether changing pulmonary pressure alters sympathetic outflow. In this pilot study, we exposed thirteen healthy humans (5 females, 28 [ ± 7] years) to high altitude hypoxia (HA; 4383m), a setting known to increase both pulmonary pressure and sympathetic activation, before selectively lowering pulmonary pressure via inhalation of the pulmonary vasodilator nitric oxide. Muscle sympathetic nerve activity (MSNA; Microneurography), blood pressure (BP; Photoplethysmography), heart rate (HR; Electrocardiogram), and peripheral oxygen saturation (SPO2; Pulse oximetry) were continually measured during ambient air breathing (Amb) and during a 6-minute inhalation of nitric oxide (iNO; 40ppm in 21% O2). Pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and stroke volume (SV) were determined via cardiac ultrasound. iNO reduced PASP (−23 ± 12%) and PVR (−21 ± 16%) compared to Amb (Table 1). iNO also reduced MSNA burst frequency (−18 ± 18%), burst incidence (−16 ± 17%) and total activity (−21 ± 20%) compared to Amb. MSNA changes during iNO were not related to changes in SPO2 (r = −0.16, P = 0.61) or MAP (r = −0.28, P = 0.35). Our data demonstrate that selectively reducing pulmonary pressure reduces sympathetic nerve activity in healthy humans; therefore, this provides evidence for a causal link in the relationship between pulmonary pressure and basal sympathetic activity. Further investigation is warranted to establish whether elevated pulmonary pressure is a mechanism contributing to chronically elevated sympathetic outflow in disease.

AB - Chronically elevated sympathetic neural activity is a characteristic of many disease states. Tonic chemoreflex activation has been implicated in the development of sympathetic overactivity; however, other reflexes may also contribute. For example, in an animal model, stimulation of pulmonary baroreceptors induces a reflex increase in sympathetic neural activity. In humans, pulmonary pressure has been shown to be related to basal sympathetic activity in pulmonary hypertension; however a critical step in determining a causal link is to establish whether changing pulmonary pressure alters sympathetic outflow. In this pilot study, we exposed thirteen healthy humans (5 females, 28 [ ± 7] years) to high altitude hypoxia (HA; 4383m), a setting known to increase both pulmonary pressure and sympathetic activation, before selectively lowering pulmonary pressure via inhalation of the pulmonary vasodilator nitric oxide. Muscle sympathetic nerve activity (MSNA; Microneurography), blood pressure (BP; Photoplethysmography), heart rate (HR; Electrocardiogram), and peripheral oxygen saturation (SPO2; Pulse oximetry) were continually measured during ambient air breathing (Amb) and during a 6-minute inhalation of nitric oxide (iNO; 40ppm in 21% O2). Pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and stroke volume (SV) were determined via cardiac ultrasound. iNO reduced PASP (−23 ± 12%) and PVR (−21 ± 16%) compared to Amb (Table 1). iNO also reduced MSNA burst frequency (−18 ± 18%), burst incidence (−16 ± 17%) and total activity (−21 ± 20%) compared to Amb. MSNA changes during iNO were not related to changes in SPO2 (r = −0.16, P = 0.61) or MAP (r = −0.28, P = 0.35). Our data demonstrate that selectively reducing pulmonary pressure reduces sympathetic nerve activity in healthy humans; therefore, this provides evidence for a causal link in the relationship between pulmonary pressure and basal sympathetic activity. Further investigation is warranted to establish whether elevated pulmonary pressure is a mechanism contributing to chronically elevated sympathetic outflow in disease.

M3 - Meeting Abstract

VL - 33

JO - Faseb Journal

JF - Faseb Journal

SN - 1530-6860

IS - Supplement 1

M1 - 562.6

T2 - Experimental Biology

Y2 - 6 April 2019

ER -