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PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex

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Science  26 Oct 2018:
Vol. 362, Issue 6413, pp. 464-467
DOI: 10.1126/science.aau6324

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Heart rate and blood pressure control

PIEZO1 and PIEZO2 are two mechanically activated ion channels that are highly expressed in lungs, bladder, and skin. Zeng et al. found that both ion channels are expressed in sensory neurons of a ganglion complex that contribute to the baroreflex, a homeostatic mechanism that helps to keep blood pressure stable (see the Perspective by Ehmke). Conditional double knockout of PIEZO1 and PIEZO2 in these neurons abolished the baroreflex and disrupted blood pressure regulation and heart rates in mice. These changes were very similar to those seen in patients with baroreflex failure. In mice, selective activation of PIEZO2-expressing ganglion neurons triggered immediate increases in heart rate and blood pressure.

Science, this issue p. 464; see also p. 398

Abstract

Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both Piezo1 and Piezo2 in the nodose and petrosal sensory ganglia of mice abolished drug-induced baroreflex and aortic depressor nerve activity. Awake, behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2-positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZO1 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control.

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