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.

Salt-sensitive hypertension (SSH) is an important and common subtype of hypertension, whose pathogenesis involves multi-level regulation, including the central nervous system (CNS), metabolic stress, and epigenetics. Dietary bioactive compounds have emerged as a research hotspot for SSH intervention due to their safety and multi-target effects. Although existing studies have focused on the CNS regulation of SSH or the role of individual dietary components, there is a lack of comprehensive analysis integrating multiple mechanisms, systematically summarizing multiple compounds, and incorporating a clinical translation perspective. This review first outlines the mechanisms of CNS pathways, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and epigenetic modifications in SSH. Then, it systematically reviews the mechanisms of action and preclinical and clinical research progress of bioactive compounds, including capsaicin, taurine, gamma-aminobutyric acid, tea, and anthocyanins in SSH. In summary, this review systematically clarifies the complex regulatory network of SSH and the intervention potential of dietary bioactive compounds from an integrated perspective, innovatively proposes a precise dietary intervention framework, and fills the research gaps in the integration of multiple mechanisms and systematic evaluation of compounds in existing studies. This framework not only provides a new integrated perspective for the basic research of SSH but also offers key references for clinical dietary guidance, functional food development, and the formulation of targeted intervention strategies.