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

Wioletta Pijacka, Davi J D A Moraes, Laura E K Ratcliffe, Angus K Nightingale, Emma C J Hart, Melina da Silva, Benedito Machado, Fiona D McBryde, Ana Paula Abdala Sheikh, Anthony Ford, Julian F R Paton

Research output: Contribution to journalArticle (Academic Journal)peer-review

80 Citations (Scopus)
298 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)1151-1159
Number of pages9
JournalNature Medicine
Volume22
Issue number10
Early online date5 Sep 2016
DOIs
Publication statusPublished - 1 Oct 2016

Structured keywords

  • CRICBristol
  • Bristol Heart Institute

Keywords

  • Hypertension
  • Preclinical research
  • Translational research

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