Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome.

Autor: Zawieja SD; Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX 77843, USA., Wang W, Wu X, Nepiyushchikh ZV, Zawieja DC, Muthuchamy M
Jazyk: angličtina
Zdroj: American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2012 Feb 01; Vol. 302 (3), pp. H643-53. Date of Electronic Publication: 2011 Dec 09.
DOI: 10.1152/ajpheart.00606.2011
Abstrakt: Numerous studies on metabolic syndrome (MetSyn), a cluster of metabolic abnormalities, have demonstrated its profound impact on cardiovascular and blood microvascular health; however, the effects of MetSyn on lymphatic function are not well understood. We hypothesized that MetSyn would modulate lymphatic muscle activity and alter muscularized lymphatic function similar to the impairment of blood vessel function associated with MetSyn, particularly given the direct proximity of the lymphatics to the chronically inflamed adipose depots. To test this hypothesis, rats were placed on a high-fructose diet (60%) for 7 wk, and their progression to MetSyn was assessed through serum insulin and triglyceride levels in addition to the expression of metabolic and inflammatory genes in the liver. Mesenteric lymphatic vessels were isolated and subjected to different transmural pressures while lymphatic pumping and contractile parameters were evaluated. Lymphatics from MetSyn rats had significant negative chronotropic effects at all pressures that effectively reduced the intrinsic flow-generating capacity of these vessels by ∼50%. Furthermore, lymphatics were remodeled to a significantly smaller diameter in the animals with MetSyn. Wire myograph experiments demonstrated that permeabilized lymphatics from the MetSyn group exhibited a significant decrease in force generation and were less sensitive to Ca(2+), although there were no significant changes in lymphatic muscle cell coverage or morphology. Thus, our data provide the first evidence that MetSyn induces a remodeling of collecting lymphatics, thereby effectively reducing their potential load capabilities and impairing the intrinsic contractility required for proper lymph flow.
Databáze: MEDLINE