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The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T7-T9 during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 [+ or -] 0.75 N/m was observed with a corresponding passive tension of 3.11 [+ or -] 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 [+ or -] 4.7 and 20.6 [+ or -] 3.2 mmHg, respectively. Subsequently, pharmacology was performed on tings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A2 analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 [+ or -] 0.63, 5.90 [+ or -] 1.4, and 6.78 [+ or -] 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by ~20% and ~40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents. lymphatic system; lymph pump; lymphangion; lymphatic smooth muscle doi: 10.1152/ajpheart.01089.2009.

In smooth muscle cells, K+ permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K+ channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K+ channels to human lymphatic vessel contractility. Thoracic ducts were harvested from 43 patients and mounted in a wire myograph for isometric force measurements or membrane potential recordings with an intracellular microelectrode. Using K+ channel blockers and activators, we demonstrate a functional contribution to human lymphatic vessel contractility from all the major classes of K+ channels [ATP-sensitive K+ (KATP), Ca2+-activated K+, inward rectifier K+, and voltage-dependent K+ channels], and this was confirmed at the mRNA level. Contraction amplitude, frequency, and baseline tension were altered depending on which channel was blocked or activated. Microelectrode impalements of lymphatic vessels determined an average resting membrane potential of --43.1 ± 3.7 mV. We observed that membrane potential changes of <5 mV could have large functional effects with contraction frequencies increasing threefold. In general, KATP channels appeared to be constitutively open since incubation with glibenclamide increased contraction frequency in spontaneously active vessels and depolarized and initiated contractions in previously quiescent vessels. The largest change in membrane voltage was observed with the KATP opener pinacidil, which caused 24 ± 3 mV hyperpolarization. We conclude that K+ channels are important modulators of human lymphatic contractility. [ABSTRACT FROM AUTHOR]