P2X3 receptor‐mediated chemoreceptor hypersensitivity in young spontaneous hypertensive rats

Abstract

Sympathetic overactivity has been related to the pathogenesis of hypertension. Enhanced peripheral chemoreceptor sensitivity has been suggested as a possible mechanism for sympathetic overactivity. We compared both baseline and chemoreflex evoked carotid sinus nerve (CSN) activity, and the electrophysiological properties of petrosal ganglion cells (PGc) innervating the carotid body in in situ preparations of young spontaneously hypertensive (SH) and Wistar rats. Since ATP plays a major role in chemosensory transduction in the carotid body, we also evaluated the contribution of ATP and P2X receptors in PGc and their involvement in sympathetic overactivity observed in SH rats. SH rats (n=22) presented: increased basal and chemoreflex evoked CSN discharge, and the electrical excitability of PGc was elevated relative to Wistar rats (n=25). A significant increase in the depolarizing effects of ATP and α,β‐methylene ATP in SH (n=18) versus Wistar (n=16) PGc was observed. This was consistent with raised single‐cell mRNA expression of ionotropic P2X3 channels (n=12) in SH rats. Moreover, both the increased baseline and chemoreflex evoked sympathetic nerve response in SH rats (n=12) was markedly reduced after perfusion of the PG with AF‐353, a selective antagonist of P2X3 receptors. Our results suggest that ATP and P2X3 receptors play an important role as a novel mechanism for increased carotid body tone and hyper‐chemosensitivy that contributes to the sympathetic overactivity in SH rats.Support: British Heart Foundation and FAPESP