# Role of Piezo1 Channels Expressed in PVN in Regulating Sympathetic Nerve Activity and Arterial Blood Pressure in Rats

## TL;DR

This study shows that Piezo1 channels in a specific brain region control sympathetic nerve activity and blood pressure in rats.

## Contribution

The study is the first to demonstrate the role of Piezo1 channels in the paraventricular nucleus in regulating sympathetic and cardiovascular function.

## Key findings

- Blocking Piezo1 channels in the PVN increased renal sympathetic nerve activity and blood pressure in a dose-dependent manner.
- Piezo1 channels are abundantly expressed in the PVN and are located in pre-sympathetic neurons projecting to the medulla.
- Activating Piezo1 channels in the PVN did not significantly alter sympathetic nerve activity or blood pressure.

## Abstract

Mechanosensitive Piezo1 channels participate in regulating pain sensitivity, insulin secretion, and vascular tension; however, their expression in the autonomic paraventricular nucleus (PVN) and role in modulating sympathetic outflow and cardiovascular function remain unstudied. In this study, unilateral PVN microinjection of the Piezo1 channel blocker Dooku1 (0.1, 1, 10, 100, and 200 pmol) administered to anesthetized male rats increased renal sympathetic nerve activity (RSNA) and mean artery pressure (MAP) in a dose-dependent manner, with maximum increases of 93 ± 30% (p < 0.0001) and 21 ± 5 mmHg (p < 0.0001), respectively, elicited by Dooku1 at 100 pmol. Similarly, PVN microinjection of the peptide Piezo1 channel blocker GsMTx4 (1 nmol) significantly increased RSNA (p < 0.001) and MAP (p < 0.0001). Conversely, PVN-microinjected Piezo1 channel activators Yoda1 (5 nmol) and Jedi2 (5 nmol) did not significantly alter RSNA or MAP. Western blot and qRT-PCR analyses of the hypothalamic PVN showed abundant Piezo1 mRNA and protein expression. Immunofluorescence detection showed that Piezo1 was expressed in pre-sympathetic PVN neurons with axons projecting to the rostral ventrolateral medulla. We conclude that Piezo1 channels expressed in the autonomic PVN neurons play an important role in regulating sympathetic outflow and cardiovascular function.