Abstract 16208: High Salt Inhibits Lymphatic Transport Function Through Regulation Of Na+-K+-ATPase Activity
Objective: Current experimental evidence suggests that the lymphatic system is emerging as a key player in the pathogenesis of salt-sensitive hypertension. In hypertensive animals, accumulation of Na+ in subcutaneous spaces stimulates VEGF-C production in macrophages, and this secretion of VEGF-C promotes hyperplasia of lymphatic capillaries. This increased density of lymphatic capillaries reduces blood pressure in response to high salt conditions. Although collecting lymphatics connected to lymphatic capillaries contribute to the transport of lymph in pathophysiological conditions, collecting lymphatic function in response to high salt levels is not clear. The present study aimed to investigate the effects of high salt on the pumping activity of lymphatics.
Methods: Afferent lymphatics were isolated from the iliac lymph nodes of Sprague-Dawley rats. The lymphatics were cannulated and pressurized to produce spontaneous lymphatic pumping activity. Changes in the frequency and diameter of lymphatic activity were measured using DVD microscopy. We used physiological salt solution (PSS) containing Na+ (146.2 mM), to which we added NaCl (10, 30, 50, and 70 mM) to increase the extra-cellular Na+ concentration.
Results: NaCl dose-dependently and significantly reduced the % frequency of lymphatic activity, indicating that NaCl induced negative chronotropic effects on the lymphatic activity. The negative effects were potentiated in the presence of ouabain (an inhibitor of Na+-K+-ATPase). Lidocaine (non-selective Na+ channel blocker) and glibenclamide (ATP-sensitive K+-channels blockers) significantly reversed the high salt-mediated reduction in lymphatic activity.
Conclusion: These results suggest that lymph containing high salt suppress lymphatic transport by inhibition of pumping, which results in excess accumulation of fluids and electrolytes in tissues. The mechanisms of high salt lymphatic transport suppression involve the regulation of Na+-K+-ATPase activity coupling with Na+ channels, and ATP-sensitive K+ channels in lymphatic smooth muscles.
- © 2012 by American Heart Association, Inc.