Bitter Taste Receptors in the Gut-Vascular Axis: A 1 Novel Target for Immune and Metabolic Regulation 2 of Hypertension

Xiaoyu Wei¹Feifei Lyu²Fuyun Jia³Lihong Zhang⁴Min Zhang^4*Qiang Xu^3*Shengyu Hua^1*

• ¹Tianjin University of Traditional Chinese Medicine, Tianjin, China
• ²The Sixth Medical Center of PLA General Hospital, 100048 Beijing, China, Beijing, China
• ³The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China., Tianjin, China
• ⁴Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China

Hypertension affects approximately 1.3 billion adults worldwide, yet the control rate remains 25 below 20%, highlighting the limitation of current therapies that primarily lower blood pressure 26 without targeting the underlying pathophysiological mechanisms. Recent research indicates that 27 bitter taste receptors, which are structurally distinct members of the G protein-coupled receptor 28 superfamily, have functions that extend beyond their traditional role in oral taste perception. These 29 receptors are extensively expressed along the gut-vascular axis, including in vascular smooth 30 muscle, cardiac tissue, macrophages, and gastrointestinal organs, thereby positioning them as 31 crucial nodes in the regulation of immunometabolic processes. This review systematically 32 elucidates the complex regulatory mechanisms of gut-vascular axis TAS2Rs in the 33 pathophysiology of hypertension and investigates TAS2R-targeting compounds, with particular 34 emphasis on their effects in modulating blood pressure. This review consolidates evidence on 35 TAS2R signaling across vascular, immune, and gastrointestinal interfaces to outline therapeutic 36 implications for hypertension.