Skin sodium, lymphatics, and blood pressure: a non-canonical mechanism of salt-sensitive hypertension

The role of lymphangiogenesis in salt-sensitive hypertension. (A) Excessive salt intake triggers the activation of the A2AR–MSK1–VEGFR2 pathway, promoting the expansion of the dermal lymphatic network, enhancing sodium clearance from the body, and protecting against blood pressure elevation. Dysregulation of this pathway, caused by decreased A2AR activation or inhibition of VEGFR2 phosphorylation, suppresses lymphangiogenesis, increases sodium retention, and raises blood pressure. The administration of an A2AR agonist may reverse this process. (B) The lymphatic vessel network also regulates blood pressure in the kidneys, but the specific role of A2AR in renal lymphangiogenesis is not yet clear.