Mesenteric lymphatic vessels adapt to mesenteric venous hypertension by becoming weaker pumps

Abstract

Lymphangions, the segments of lymphatic vessels between two adjacent lymphatic valves, actively pump lymph. Acute changes in transmural pressure and lymph flow have profound effects on lymphatic pump function in vitro. Chronic changes in pressure and flow in vivo have also been reported to lead to significant changes in lymphangion function. Because changes in pressure and flow are both cause and effect of adaptive processes, characterizing adaptation requires a more fundamental analysis of lymphatic muscle properties. Therefore, the purpose of the present work was to use an intact lymphangion isovolumetric preparation to evaluate changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca(2+) in response to sustained mesenteric venous hypertension. Bovine mesenteric veins were surgically occluded to create mesenteric venous hypertension. Postnodal mesenteric lymphatic vessels from mesenteric venous hypertension (MVH; n = 6) and sham surgery (Sham; n = 6) animals were isolated and evaluated 3 days after the surgery. Spontaneously contracting MVH vessels generated end-systolic active tension and end-diastolic active tension lower than the Sham vessels. Furthermore, steady-state active tension and intracellular Ca(2+) concentration levels in response to KCl stimulation were also significantly lower in MVH vessels compared with those of the Sham vessels. There was no significant difference in passive tension in lymphatic vessels from the two groups. Taken together, these results suggest that following 3 days of mesenteric venous hypertension, postnodal mesenteric lymphatic vessels adapt to become weaker pumps with decreased cytosolic Ca(2+) concentration.

Lymphangiogenic therapy prevents cardiac dysfunction by ameliorating inflammation and hypertension

“…Our observations are in line with these previous studies; however, the studies presented herein importantly assess lymphatic dysfunction in the absence of direct injury or surgical manipulation. Likely the impairments in lymphatic vascular function observed in angiotensin II-infused mice could come directly from angiotensin II actions on the endothelium, as angiotensin II can induce endothelial dysfunction ( Gomolak and Didion, 2014 ; Watanabe et al, 2005 ) or perhaps indirectly from angiotensin II infusion-induced hypertension, which reportedly alters lymphatic vascular function ( Dongaonkar et al, 2015 ).…”

Lymphatic Network in Atherosclerosis: the Underestimated Path

“…Therefore, a recent study by Dongaonkar  et al. attested the changes in mesenteric lymphatic muscle mechanical properties and the intracellular Ca 2+ in response to sustained mesenteric venous hypertension [56]. They showed that following 3 days of mesenteric venous hypertension, the adaptive response of postnodal mesenteric lymphatic vessels resulted in weaker pumps with decreased cytosolic Ca 2+ concentration.…”

Lymphatic Vessel Network Structure and Physiology

“…Portal hypertension may also detrimentally affect mesenteric lymph flow. Experimental venous hypertension for several days was reported to cause a decrease in bovine mesenteric lymphatic vessel contractions, in association with decreased [Ca 2+ ] i (275). A sizeable number of other scenarios that could influence lymph composition and flow from the gut remain to be studied, yet it is clear that lymphatic vessels have a key role in the development of either local or systemic inflammation in response to the conditions in the gut.…”