Lymphatics and the Pathogenesis of Hypertension

Within the pages of Lymphatic Research and Biology we have long promoted the concept of the lymphatic continuum, ^1–3 in which there is an emphasis upon contributory lymphatic mechanisms to the initiation, maintenance, natural history, or therapeutic approach to a broad array of systemic diseases. Thus, quite appropriately, in this issue of the journal, Chachaj and colleagues extend this form of consideration to the pathogenesis of human hypertension.

This human investigation is based upon prior studies of animal models of hypertension in which it has been observed that extrarenal control of sodium balance and blood pressure can reside in the negatively charged glycosaminoglycans, macrophages and lymphatic vessels of the skin. Sodium ions in the skin interstitium can be stored in an osmotically inactive form bound to glycosaminoglycans (GAGs).^4,5 The latter can provide an actively regulated interstitial Na+ exchange mechanism that participates in volume and blood pressure homeostasis. ⁶ 23Na magnetic resonance imaging of human bodily sodium distribution demonstrates that sodium is primarily accumulated in the skin and muscles. ⁷

In their investigation, Chachaj et al. examined surgical skin biopsies from 91 subjects, both hypertensive and controls. The groups with and without hypertension differed in cutaneous expression of CD68, and in their plasma concentrations of VEGF-C. The results of this investigation suggest that cutaneous accumulation of Na+ is associated with the presence of hypertension and is also correlated with the presence of CD68 macrophages and with decreased prevailing levels of VEGF-C, implicating the lymphatic contribution to this cascade of events leading to the presence of hypertension.

These human observations are provocative and suggest that further exploration of the lymphatic contribution to the pathogenesis and maintenance of hypertension might lead to novel interventions directed at the prevention and treatment of this highly morbid condition.