The influence of pulmonary arterial mechanoreceptors on sympathoexcitation in hypoxia.

Abstract

The main aim of this thesis is to characterise the effect of afferent feedback from pressure sensitive receptors (mechanoreceptors) located in the pulmonary arteries on sympathetic neural activity, autonomic regulation of blood pressure and respiratory modulation of sympathetic outflow (MSNA) in conditions with elevated pulmonary arterial pressure (e.g. exercise and high altitude) in healthy individuals. To address this aim, sympathetic neural activity to the skeletal muscle vasculature was assessed via microneurography, baroreflex control of MSNA (vascular sympathetic baroreflex) via the modified Oxford test and spontaneous arterial baroreflex and respiratory modulation of MSNA by dividing resting MSNA into two phases: expiration and inspiration. Experimental study 1 examines the influence of pulmonary arterial mechanoreceptors on sympathetic neural activity and spontaneous arterial baroreflex function during moderate intensity exercise in acute hypoxia. Experimental study 2 examines whether engagement of the peripheral chemoreceptor reflex interacts with the contribution of pulmonary arterial mechanoreceptors on sympathetic neural activity during several days (6-9) of high altitude hypoxia in healthy individuals. Experimental study 3 examines the influence of pulmonary arterial mechanoreceptors on respiratory modulation of MSNA during several days of high altitude hypoxia in healthy individuals and the influence of enhanced minute ventilation by peripheral chemoreflex activation on respiratory modulation of MSNA during several days (6-9) of high altitude hypoxia in healthy individuals. This thesis demonstrates that unloading of pulmonary arterial mechanoreceptors during hypoxic exercise at a maintained intensity reduces sympathetic outflow without influencing spontaneous vascular baroreflex gain. Reducing pulmonary arterial pressure by nitric oxide inhalation with clamped end tidal O2 and CO2 decreases sympathetic outflow in rest at high altitude. Thus, the influence of pulmonary arterial mechanoreceptors on sympathetic outflow and vascular baroreflex gain is consistent in exercise and high altitude hypoxia, two conditions that elevate pulmonary arterial pressure. Furthermore, unloading pulmonary arterial mechanoreceptors while suppressing the peripheral chemoreflex (low dose infusion of dopamine) provokes a smaller reduction in MSNA compared with non-suppressed peripheral chemoreflex. This smaller effect may reflect the vascular action of the method used to suppress peripheral chemoreflex and compensatory vascular sympathetic baroreflex engagement. Thus, pulmonary arterial mechanoreceptors influence sympathetic outflow but not vascular baroreflex gain in conditions with elevated pulmonary arterial pressure, which may operate independently of peripheral chemoreflex engagement. This thesis also demonstrates, for the first time, that unloading pulmonary arterial mechanoreceptors increases respiratory modulation of MSNA at high altitude. The increase in respiratory modulation of MSNA may be caused by enhanced sympathetic inhibition during inspiration. Furthermore, lower minute ventilation and reduced arterial blood pressure have no effect on respiratory modulation of MSNA with elevated pulmonary arterial pressure at high altitude. Together, the findings of this thesis demonstrate that pulmonary arterial mechanoreceptors increase sympathetic outflow during exercise and in rest at high altitude and reduce the magnitude of respiratory modulation of MSNA. Thus, pulmonary arterial mechanoreceptors are an unrecognised mechanism involved in cardiovascular control in conditions with elevated pulmonary arterial pressure.

Date of Award	29 Aug 2025
Original language	English
Awarding Institution	Bangor University
Supervisor	Jonathan Moore (Supervisor), Mike Stembridge (Supervisor) & Sam Oliver (Supervisor)