BBB seminar: Tine Veronica Karlsen
The skin as a player in salt-induced hypertension
Tine Veronica Karlsen
Department of Biomedicine, University of Bergen
Hypertension is a major risk factor for stroke, coronary heart disease and heart failure, accounting for 18% of cardiovascular disease deaths in the Western world. Salt and hypertension have been linked since ancient times, but the role of salt in the pathogenesis of arterial hypertension is still poorly understood and much debated. The kidneys play a central role in body volume and blood pressure homeostasis by balancing excretion of sodium with intake, thus preventing excessive water retention volume expansion and subsequent blood pressure rise. Nevertheless, recent studies in humans and rodents have revealed that sodium handling is not only a kidney affair, as sodium is stored in skin without commensurate water retention, questioning the notion that sodium and water are always retained in parallel. According to these studies, immune cells in the skin microenvironment sense stored sodium, become activated and induce growth of new lymphatics as well as increase nitric oxide (NO) synthesis in small blood vessels. Furthermore, this chain of events influences the systemic blood pressure in salt-induced hypertension in experiments with mice.
Based on these new, intriguing findings, we aim to further explore how the skin microenvironment, including the interstitium, immune cells and lymphatics, take part in extra-renal regulation of blood volume and blood pressure homeostasis, and thus contribute in the pathogenesis of hypertension. We have addressed whether skin sodium storage in salt-sensitive hypertension affects local osmolarity, as even small osmotic gradients between plasma and interstitium would represent a substantial force for fluid filtration and edema formation. Our finding of osmotic gradients within the skin, led us to initial studies where we characterize various immune cell populations in different skin layers and draining lymph nodes to assess the effect of local salt storage. We hypothesize that antigen-presenting cells may act as the link between local and systemic salt effects. After confirming that salt-sensitive hypertension results in lymphangiogenesis, we have performed studies to assess the functionality of the expanded lymphatic network with respect to lymph transport capacity and contractility, and as conduits for antigen-presenting cells travelling to the lymph nodes for antigen presentation.
Chairperson: Meg Veruki, Department of Biomedicine