The acute effects of pulmonary artery pressure lowering on muscle sympathetic nerve activity in pulmonary hypertension

Sympatho-excitation in pulmonary arterial hypertension (PAH) is associated with poorer clinical outcomes including worsened exercise capacity and the risk of clinical deterioration. This sympathetic nerve activity (SNA) may promote adverse remodelling in pulmonary arteries and exacerbate pulmonary vasoconstriction. However, the drivers of sympathatho-excitation in pulmonary hypertension (PH) remain incompletely defined. Pulmonary baroreceptors respond to increases in pulmonary arterial pressure and distension causing reflex increases in sympathetic outflow. We tested the hypothesis that activation of pulmonary baroreceptors increases muscle SNA (MSNA) in patients with PH (PAH and chronic thrombo-embolic PH [CTEPH]). We recruited 9 PAH and 1 CTEPH patients (6 female; age 52±13 years; mean±SD). Microneurography recording of MSNA was made from the peroneal nerve (n=8) for a 10 min baseline resting period, and for a 10 min period following nebulisation of iloprost (a synthetic prostacyclin; 5 μg) to reduce pulmonary artery pressure selectively. Using transthoracic echocardiography, mean pulmonary artery pressure (mPAP) was estimated from pulmonary arterial acceleration time, and systolic pulmonary artery pressure (sPAP), estimated from tricuspid regurgitant velocity, both at baseline and after iloprost. Measures at baseline and following iloprost were compared using Student’s paired t -test. mPAP and sPAP were reduced with iloprost compared to baseline (21±5 vs. 28±6 mmHg, p<0.001 and 45±16 vs. 52±19 mmHg, p=0.032 respectively). Overall, MSNA burst frequency, burst incidence, burst amplitude and total activity were unchanged following iloprost (all p>0.05). However, burst amplitude and consequently total activity were reduced with iloprost in half of the participants. These participants had higher baseline MSNA burst amplitude (50±7 vs. 32±6 % of largest burst; p=0.016) that correlated with a larger reduction in burst amplitude following iloprost (linear logistic regression, R 2 =0.547; p=0.036), and had higher baseline total activity (1809±547 vs. 833±212 au; p=0.031). Pulmonary baroreceptors are unlikely the predominant contributor to MSNA in PH but may augment sympathetic burst amplitude and total activity in patients with higher baseline MSNA. Whether this drives clinically relevant adverse pulmonary vascular remodelling and vasoconstriction warrants further investigation. Heart Lung Foundation (formerly Greenlane Research and Educational Fund; Ref# 21/01/4153; M.J.P, J.F.R.P, S.S, and J.P.F) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.