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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Calcium sensitivity and cooperativity of permeabilized rat mesenteric lymphatics

¹Department of Systems Biology and Translational Medicine, Cardiovascular Research Institute, Division of Lymphatic Biology, Texas A&M Health Science Center College of Medicine, College Station, Texas; and ²Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, Missouri

Submitted 12 December 2007 ; accepted in final form 26 February 2008

Lymphatic muscle contraction is critical for the centripetal movement of lymph that regulates fluid balance, protein homeostasis, lipid absorption, and immune function. We have demonstrated that lymphatic muscle has both smooth and striated muscle contractile elements; however, the basic contractile properties of this tissue remain poorly defined. We hypothesized that contractile characteristics of lymphatic myofilaments would be different from vascular smooth muscle myofilaments. To test this hypothesis, –log[Ca²⁺] (pCa)-tension relationship was determined for -toxin permeabilized mesenteric lymphatics, arteries, and veins. The Ca²⁺ sensitivity (pCa₅₀) of mesenteric lymphatics was significantly lower compared with arteries (6.16 ± 0.05 vs. 6.44 ± 0.02; P < 0.05), whereas there was no difference in pCa₅₀ between lymphatics and veins (6.16 ± 0.05 vs. 6.00 ± 0.10; not significant). The Hill coefficient for -toxin-permeabilized lymphatics was not significantly different from arteries but was significantly greater than that of the veins (1.98 ± 0.19 vs. 1.21 ± 0.18; P < 0.05). In addition, the maximal tension and pCa₅₀ values were significantly greater in -toxin-permeabilized lymphatics compared with β-escin-permeabilized lymphatics (0.27 ± 0.03 vs. 0.15 ± 0.01 and 6.16 ± 0.05 vs. 5.86 ± 0.06 mN/mm, respectively; P < 0.05), whereas the Hill coefficient was significantly greater in β-escin-permeabilized lymphatics. Western blot analyses revealed that CPI-17 levels were significantly decreased by about 50% in β-escin-permeabilized lymphatics, compared with controls, whereas no change in the level of calmodulin was detected. Our data constitute the first description of the pCa-tension relationship in permeabilized lymphatic muscle. It suggests that differences in myofilament Ca²⁺ sensitivity and cooperativity among lymphatic muscle and vascular smooth muscles contribute to the functional differences that exist between these tissues.

lymphatic muscle; pCa-force relationship; calcium sensitivity