Post-nodal lymphatic vessels adapt to sustained high flow conditions by becoming weaker pumps
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abstract
Edemagenic challenges can make passive lymph flow so high that active lymphatic vessel pumping may not be necessary to propel lymph. Indeed, an acute increase in lymph flow is reported to decrease lymphatic contraction frequency and strength in vitro. However, the lymphatic response to a chronic increase in flow in vivo is unknown. We hypothesized that lymphatic vessels become weaker pumps when exposed to a sustained increase in lymph flow. We surgically occluded bovine mesenteric veins to create mesenteric venous hypertension and high lymph flow conditions. Three days after surgery, postnodal mesenteric lymphatic vessels (MVH) were isolated and compared to vessels from sham surgery animals (SHAM) to quantify changes in function, biomechanics, calcium homeostasis and gene expression. Compared to SHAM, MVH vessels exhibited a lower pump index, active tension, K+ induced cytosolic [Ca2+], as well as a lower expression of SERCA type 3, voltagedependent Ca2+ channel, and voltagegated K+ channel regulatory genes. In short, postnodal lymphatic vessels adapt to high flow conditions by becoming weaker pumps. The present work is the first to integrate experimental approaches at the tissue, cellular, and molecular levels to relate the mechanisms of adaptation to biomechanical and functional responses to clinicallyrelevant edemagenic stimuli. (Supported by NIH and AHA)
