Novel ideas about salt, blood pressure, and pregnancy.

The molecular mechanisms leading to preeclampsia are poorly understood. It has been related to certain immune mechanisms, as well as the pathological regulation of the renin-angiotensin system together with perturbed salt and plasma volume regulation. Finally, a non-specific, vascular, inflammatory response is generated, which leads to the clinical syndrome. Here, we present novel findings in salt (NaCl) metabolism implying that salt is not only important in blood pressure control and volume homeostasis, but also in immune regulation. Sodium and chloride can be stored without accumulation of water in the interstitium at hypertonic concentrations through interactions with proteoglycans. Macrophages in the interstitium act as osmosensors for salt, producing increased amounts of vascular endothelial factor C, which increases the density of the lymph-capillary network and the production of nitric oxide in vessels. An increased interstitial salt concentration activates the innate immune system, especially Th17 cells, and may be an important trigger for autoimmune diseases. The novel findings with the idea of sodium storage and local mechanisms of volume and immune regulation are appealing for preeclampsia and may unify the "immune" and "vascular" hypotheses of preeclampsia.