Transient Receptor Potential Channel Signaling in Hypertension: Mechanisms, Translation, and Therapeutic Targeting.

Abstract

Arterial hypertension (HT) is a major risk factor in the pathogenesis of cardiovascular diseases and has a high prevalence. The pathogenesis of primary HT, which accounts for the majority of HT cases, has not been fully elucidated; therefore, effective treatment targets remain an important area of research. Transient receptor potential (TRP) channels represent a distinct class of cation channels that play a pivotal role in signal transduction by altering membrane potential or intracellular Ca2+ concentration. Based on sequence similarity, TRP channels are classified into six subfamilies: TRP canonical (TRPC), TRP melastatin (TRPM), TRP vanilloid (TRPV), TRP mucolipin (TRPML), TRP ankyrin (TRPA), and TRP polycystin (TRPP). These channels exhibit broad expression across diverse tissues and cell types and play critical roles in numerous pathophysiological processes through the regulation of ion concentrations (Ca2+, Mg2+, Na+, and K+) and the modulation of intracellular signal transduction pathways. Research involving human subjects, as well as experimental models, highlights the essential role of TRP channels in maintaining vascular homeostasis and regulating blood pressure. TRP channels, particularly TRPCs, have gained increasing attention for their role in resistant HT, a condition in which blood pressure remains uncontrolled despite the use of multiple antihypertensive drugs. Additionally, these channels have been identified as central mediators of inflammation and oxidative stress, processes that are pivotal in the pathogenesis of cardiovascular disorders, including HT. This review summarizes current evidence on TRPC, TRPV, and TRPM channels in HT, highlighting emerging translational findings and potential therapeutic implications.