Skin Lymphatic System in the Pathogenesis of Arterial Hypertension – Review and Critique

Although numerous studies have confirmed the relationship between high salt intake and elevated blood pressure, the exact molecular mechanisms of this relationship are still unclear. There is growing evidence that skin interstitium, as well as the skin lymphatic system, are important regulators of both sodium (Na+) balance and blood pressure. Skin is in itself a large reservoir of Na+ ions which are stored in an osmotically inactive form on glycosaminoglycans (GAGs). Local hypertonicity due to extensive accumulation of Na+ within the skin as a result of a high-salt diet was demonstrated to induce macrophages to express a transcription factor termed tonicityresponsive enhancer binding protein (TonEBP) and subsequently to secrete vascular endothelial growth factor-C (VEGF-C), activating lymphangiogenesis within the skin. This regulatory axis seems to be adaptive in maintaining blood pressure in high salt-load states. Recent studies have added new insights into the functioning of lymphatic vessels and the pathogenesis of salt-sensitive hypertension as well as questioned the classic view of Na+ homeostasis. This review aims to summarize recent findings pertaining to the involvement of the skin lymphatic system in Na+ and blood pressure regulation.