P2X3 receptor targeting in the carotid body for regulating hypertension: a transla...
| Full text | |
| Author(s): Show less - |
Pijacka, Wioletta
;
Moraes, Davi J. A.
;
Ratcliffe, Laura E. K.
;
Nightingale, Angus K.
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Hart, Emma C.
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da Silva, Melina P.
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Machado, Benedito H.
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McBryde, Fiona D.
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Abdala, Ana P.
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Ford, Anthony P.
;
Paton, Julian F. R.
Total Authors: 11
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| Document type: | Journal article |
| Source: | Nature Medicine; v. 22, n. 10, p. 1151-1159, OCT 2016. |
| Web of Science Citations: | 46 |
| 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. (AU) | |
| FAPESP's process: | 13/06077-5 - Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia |
| Grantee: | Benedito Honorio Machado |
| Support type: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/10484-5 - Electrophysiological and molecular characterization of neurons involved in the generation of respiratory rhythm and pattern of rats during postnatal development |
| Grantee: | Davi José de Almeida Moraes |
| Support type: | Research Grants - Young Investigators Grants |