The regulation of pulmonary vascular tone by neuropeptides and the implications for pulmonary hypertension

Lo, CCW; Moosavi, SM; Bubb, KJ

The regulation of pulmonary vascular tone by neuropeptides and the implications for pulmonary hypertension

Lo, CCW Moosavi, SM

Bubb, KJ

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Publication Type:: Journal Article
Citation:: Frontiers in Physiology, 2018, 9 (AUG)
Issue Date:: 2018-08-23

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Field	Value	Language
dc.contributor.author	Lo, CCW	en_US
dc.contributor.author	Moosavi, SM https://orcid.org/0000-0002-0905-3825	en_US
dc.contributor.author	Bubb, KJ	en_US
dc.date.issued	2018-08-23	en_US
dc.identifier.citation	Frontiers in Physiology, 2018, 9 (AUG)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130315
dc.description.abstract	© 2018 Lo, Moosavi and Bubb. Pulmonary hypertension (PH) is an incurable, chronic disease of small pulmonary vessels. Progressive remodeling of the pulmonary vasculature results in increased pulmonary vascular resistance (PVR). This causes secondary right heart failure. PVR is tightly regulated by a range of pulmonary vasodilators and constrictors. Endothelium-derived substances form the basis of most current PH treatments. This is particularly the case for pulmonary arterial hypertension. The major limitation of current treatments is their inability to reverse morphological changes. Thus, there is an unmet need for novel therapies to reduce the morbidity and mortality in PH. Microvessels in the lungs are highly innervated by sensory C fibers. Substance P and calcitonin gene-related peptide (CGRP) are released from C-fiber nerve endings. These neuropeptides can directly regulate vascular tone. Substance P tends to act as a vasoconstrictor in the pulmonary circulation and it increases in the lungs during experimental PH. The receptor for substance P, neurokinin 1 (NK1R), mediates increased pulmonary pressure. Deactivation of NK1R with antagonists, or depletion of substance P prevents PH development. CGRP is a potent pulmonary vasodilator. CGRP receptor antagonists cause elevated pulmonary pressure. Thus, the balance of these peptides is crucial within the pulmonary circulation (Graphical Abstract). Limited progress has been made in understanding their impact on pulmonary pathophysiology. This is an intriguing area of investigation to pursue. It may lead to promising new candidate therapies to combat this fatal disease. This review provides a summary of the current knowledge in this area. It also explores possible future directions for neuropeptides in PH.	en_US
dc.relation.ispartof	Frontiers in Physiology	en_US
dc.relation.isbasedon	10.3389/fphys.2018.01167	en_US
dc.title	The regulation of pulmonary vascular tone by neuropeptides and the implications for pulmonary hypertension	en_US
dc.type	Journal Article
utslib.citation.volume	AUG	en_US
utslib.citation.volume	9	en_US
utslib.for	0606 Physiology	en_US
utslib.for	1116 Medical Physiology	en_US
utslib.for	1701 Psychology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access
pubs.issue	AUG	en_US
pubs.publication-status	Published	en_US
pubs.volume	9	en_US

Abstract:

© 2018 Lo, Moosavi and Bubb. Pulmonary hypertension (PH) is an incurable, chronic disease of small pulmonary vessels. Progressive remodeling of the pulmonary vasculature results in increased pulmonary vascular resistance (PVR). This causes secondary right heart failure. PVR is tightly regulated by a range of pulmonary vasodilators and constrictors. Endothelium-derived substances form the basis of most current PH treatments. This is particularly the case for pulmonary arterial hypertension. The major limitation of current treatments is their inability to reverse morphological changes. Thus, there is an unmet need for novel therapies to reduce the morbidity and mortality in PH. Microvessels in the lungs are highly innervated by sensory C fibers. Substance P and calcitonin gene-related peptide (CGRP) are released from C-fiber nerve endings. These neuropeptides can directly regulate vascular tone. Substance P tends to act as a vasoconstrictor in the pulmonary circulation and it increases in the lungs during experimental PH. The receptor for substance P, neurokinin 1 (NK1R), mediates increased pulmonary pressure. Deactivation of NK1R with antagonists, or depletion of substance P prevents PH development. CGRP is a potent pulmonary vasodilator. CGRP receptor antagonists cause elevated pulmonary pressure. Thus, the balance of these peptides is crucial within the pulmonary circulation (Graphical Abstract). Limited progress has been made in understanding their impact on pulmonary pathophysiology. This is an intriguing area of investigation to pursue. It may lead to promising new candidate therapies to combat this fatal disease. This review provides a summary of the current knowledge in this area. It also explores possible future directions for neuropeptides in PH.

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http://hdl.handle.net/10453/130315