The carotid chemoreceptor contributes to the elevated arterial stiffness and vasoconstrictor outflow in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) patients have increased central arterial stiffness and muscle sympathetic nervous activity (MSNA), both of which contribute to cardiovascular (CV) dysfunction and increased CV risk. Previous work suggests that COPD patients have elevated carotid chemoreceptor (CC) activity/sensitivity, which may contribute to the elevated MSNA and arterial stiffness. Accordingly, the effect of CC inhibition on central arterial stiffness, MSNA and CV function at rest in COPD patients was examined in a randomized placebo-controlled study. Thirteen mild-moderate COPD patients (forced expired volume in 1 s (FEV ) predicted ± SD: 83 ± 18%) and 13 age- and risk-matched controls completed resting CV function measurements with either i.v. saline or i.v. dopamine (2 μg kg min ) while breathing normoxic or hyperoxic air (100% O ). On a separate day, a subset of COPD patients and controls completed MSNA measurements while breathing normoxic or hyperoxic air. Arterial stiffness was determined by pulse-wave velocity (PWV) and MSNA was measured by microneurography. Brachial blood flow was determined using Doppler ultrasound, cardiac output was estimated by impedance cardiography, and vascular conductance was calculated as flow/mean arterial pressure (MAP). CC inhibition with dopamine decreased central and peripheral PWV, and MAP (P < 0.05) while increasing vascular conductance in COPD. No change in CV function was observed with dopamine in controls. CC inhibition with hyperoxia decreased peripheral PWV and MSNA (P < 0.05) in COPD, while no change was observed in controls. CC inhibition decreased PWV and MSNA, and improved vascular conductance in COPD, suggesting that tonic CC activity is elevated at rest and contributes to the elevated arterial stiffness in COPD.

Carotid chemoreceptors: the link between pulmonary and cardiovascular disease?

“…Patients in this study also demonstrated greater vascular conductance of the brachial artery during dopamine infusion, probably attributable to a reduction in mean arterial pressure (Table 3 in Phillips et al . ). In line with this notion, muscle sympathetic nerve activity during hyperoxia was reduced in the subset of seven patients with COPD.…”

“…In conclusion, Phillips et al . () advance our understanding of the relationship between carotid chemoreceptors, muscle sympathetic nerve activity and vascular function in patients with COPD. The authors show for the first time that reducing carotid chemoreceptor activity leads to attenuation of central and peripheral artery stiffness as well as greater vasodilatation in distal conduit arteries of patients with COPD.…”

“…The cascade of biochemical reactions linking hypoxaemia, sympathetic nervous system activity and cardiovascular regulation has, to date, remained poorly understood in COPD. Therefore, a recent study published in this issue of The Journal of Physiology by Phillips and colleagues () attempted to resolve one important piece of this puzzle. Specifically, authors used a single‐blind, placebo‐controlled cross‐over design which investigated carotid chemoreceptor sensitivity in 13 patients with mild–moderate COPD (GOLD Stages 1 and II, not prescribed oxygen therapy).…”

“…Targeting the carotid chemoreceptors as a means to improve health‐related outcomes is a new and exciting field of biomedical research which has yielded promising results. While Phillips and colleagues () provide novel insight into this field, nitric oxide (NO), historically known for its robust vasodilatory effects, has also been shown to blunt carotid chemoreceptor activity in preclinical and human models. For example, chronic supplementation of inorganic nitrate in the form of beetroot juice increases circulating NO bioavailability via the nitrate‐nitrite‐nitric oxide pathway, and has been show to attenuate carotid chemoreflex sensitivity (Bock et al .…”

“…Interestingly, and of relevance to Phillips et al . (), CPAP therapy attenuates the ventilatory response to hypoxia (carotid chemoreflex sensitivity), increases NO bioavailability which reduces carotid chemoreceptor activity, and ultimately lowers sympathetic nerve activity. Taken together, these studies suggest the link between lower carotid chemoreflex sensitivity and vascular health in patient populations (i.e.…”