Purinergic receptors in the carotid body as a new drug target for controlling hypertension

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dc.contributor.author Pijacka, W en
dc.contributor.author Moreas, DJA en
dc.contributor.author Ratcliffe, LEK en
dc.contributor.author Nightingale, AK en
dc.contributor.author Hart, EC en
dc.contributor.author da Silva, MP en
dc.contributor.author Machado, BH en
dc.contributor.author McBryde, Fiona en
dc.contributor.author Abdala, AP en
dc.contributor.author Ford, AP en
dc.contributor.author Paton, Julian en
dc.date.accessioned 2016-10-18T21:43:10Z en
dc.date.issued 2016-10 en
dc.identifier.citation Nature Medicine, 2016, 22(10), pp. 1151-1159 en
dc.identifier.issn 1078-8956 en
dc.identifier.uri http://hdl.handle.net/2292/30797 en
dc.description.abstract In view of the high proportion of individuals with resistance to antihypertensive medication and/or poor compliance or tolerance of this medication, new drugs to treat hypertension are urgently needed. Here we show that peripheral chemoreceptors generate aberrant signaling that contributes to high blood pressure in hypertension. We discovered that purinergic receptor P2X3 (P2rx3, also known as P2x3) mRNA expression is upregulated substantially in chemoreceptive petrosal sensory neurons in rats with hypertension. These neurons generate both tonic drive and hyperreflexia in hypertensive (but not normotensive) rats, and both phenomena are normalized by the blockade of P2X3 receptors. Antagonism of P2X3 receptors also reduces arterial pressure and basal sympathetic activity and normalizes carotid body hyperreflexia in conscious rats with hypertension; no effect was observed in rats without hypertension. We verified P2X3 receptor expression in human carotid bodies and observed hyperactivity of carotid bodies in individuals with hypertension. These data support the identification of the P2X3 receptor as a potential new target for the control of human hypertension. en
dc.description.uri http://www.nature.com/nm/index.html en
dc.publisher Nature Publishing Group en
dc.relation.ispartofseries Nature Medicine en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1078-8956/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Purinergic receptors in the carotid body as a new drug target for controlling hypertension en
dc.type Journal Article en
dc.identifier.doi 10.1038/nm.4173 en
pubs.begin-page 1151 en
pubs.volume 22 en
dc.rights.holder Copyright: Nature Publishing Group en
dc.identifier.pmid 27595323 en
pubs.author-url http://www.nature.com/nm/journal/v22/n10/full/nm.4173.html en
pubs.end-page 1159 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 538275 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Physiology Division en
dc.identifier.eissn 1546-170X en
pubs.record-created-at-source-date 2016-08-09 en
pubs.dimensions-id 27595323 en

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