Inhibition of the active lymph pump by flow in rat mesenteric lymphatics and thoracic duct

Abstract

There are only a few reports of the influence of imposed flow on an active lymph pump under conditions of controlled intraluminal pressure. Thus, the mechanisms are not clearly defined. Rat mesenteric lymphatics and thoracic ducts were isolated, cannulated and pressurized. Input and output pressures were adjusted to impose various flows. Lymphatic systolic and diastolic diameters were measured and used to determine contraction frequency and pump flow indices. Imposed flow inhibited the active lymph pump in both mesenteric lymphatics and in the thoracic duct. The active pump of the thoracic duct appeared more sensitive to flow than did the active pump of the mesenteric lymphatics. Imposed flow reduced the frequency and amplitude of the contractions and accordingly the active pump flow. Flow-induced inhibition of the active lymph pump followed two temporal patterns. The first pattern was a rapidly developing inhibition of contraction frequency. Upon imposition of flow, the contraction frequency immediately fell and then partially recovered over time during continued flow. This effect was dependent on the magnitude of imposed flow, but did not depend on the direction of flow. The effect also depended upon the rate of change in the direction of flow. The second pattern was a slowly developing reduction of the amplitude of the lymphatic contractions, which increased over time during continued flow. The inhibition of contraction amplitude was dependent on the direction of the imposed flow, but independent of the magnitude of flow. Nitric oxide was partly but not completely responsible for the influence of flow on the mesenteric lymph pump. Exposure to NO mimicked the effects of flow, and inhibition of the NO synthase by N (G)-monomethyl-L-arginine attenuated but did not completely abolish the effects of flow.

Figure 1. The effect of imposed flow on the contractions of rat mesenteric lymphatics

A, the input and output pressures are 5 cmH₂O, imposed flow gradient 0 cmH₂O. B, input pressure 8.5 cmH₂O, output pressure 1.5 cmH₂O, imposed flow gradient 7 cmH₂O.

Figure 2. Effects of imposed flow on parameters of active pump in rat mesenteric lymphatics

A, increasing flow from the imposed transaxial pressure gradient increases the lymphatic systolic diameter dramatically and results in subtle increases in diastolic diameter (diameters normalized to the passive diameter at 0 cmH₂O pressure gradient condition). B, the increasing flow produces a strong inhibition of the lymphatic contraction frequency (normalized to the zero pressure gradient condition). C, the strength of the lymphatic contractions as measured by the ejection fraction is strongly attenuated by increasing flows. D, these effects combine to produce a strong inhibition of the lymph pump by increasing imposed flow. * Significant difference of parameters between no-flow conditions and the level of imposed pressure gradient (P < 0.05, n = 7).

Figure 3. Effects of imposed flow on parameters of active pump in rat thoracic duct

A, a potent inhibition of the lymphatic contraction by increasing imposed flow results in increases of the lymphatic systolic diameter. Again, increasing imposed flow results in small increases in the thoracic duct diastolic diameter (diameters normalized to the passive diameter at 0 cmH₂O pressure gradient condition). B, the increasing flow produces a nearly complete inhibition of the lymphatic contraction frequency (normalized to the zero pressure gradient condition). C, the thoracic duct ejection fraction is about half that of the mesenteric lymphatic pump and is very strongly attenuated by increasing flows. D, these effects combine to produce an extremely strong inhibition of the lymph pump by increasing imposed flow. * Significant difference of parameters between no-flow conditions and the level of imposed pressure gradient (P < 0.05, n = 9).

Figure 4. The temporal pattern of the parameters of active pump in rat mesenteric lymphatics during orthograde and retrograde imposed flows (+1 and −1 cmH₂O imposed transaxial pressure gradients)

A, the normalized lymphatic systolic diameter increases slowly over 5 min after the imposition of flows of +1 cmH₂O (▪, n = 9) and −1 cmH₂O (□, n = 11). B, the imposition of flows produces a rapid inhibition of the lymphatic contraction frequency that slowly returns towards the values seen before the imposition of flow. C, the strength of the lymphatic contractions as measured by the ejection fraction slowly falls after the imposition of flows. D, these effects combine to produce a sustained inhibition of the lymph pump by imposed flow. * Significant difference between parameters in no-flow conditions and specified minute of imposed flow (P < 0.05). All parameters normalized to the 0 cmH₂O pressure gradient condition.

Figure 5. The temporal pattern of the parameters of active pump in rat mesenteric lymphatics during orthograde and retrograde imposed flows (+3 and −3 cmH₂O imposed transaxial pressure gradients)

A, the normalized lymphatic systolic diameter increases over 5 min after the imposition of flows of +3 cmH₂O (▪, n = 12) and −3 cmH₂O (□, n = 7). B, the imposition of flows produces a rapid potent inhibition of the lymphatic contraction frequency that returns towards control values. C, the ejection fraction slowly falls after the imposition of flows. D, these effects also combine to produce a sustained inhibition of the lymph pump by imposed flow. * Significant difference between parameters in no-flow conditions and specified minute of imposed flow (P < 0.05). All parameters normalized to the 0 cmH₂O pressure gradient condition.

Figure 6. The flow-induced inhibition of contraction frequency in lymphatics depends on the speed at which the changes in the direction of flow occur

A rapid change in the imposed flow direction temporarily ameliorates the preceding flow-mediated inhibition of the contraction frequency and fractional pump flow in rat mesenteric lymphatics. During slow changes in the flow direction, retrograde flow immediately causes a flow-mediated inhibition of parameters of the active lymph pump. (The dashed line indicates changing the imposed flow directly from the orthograde to retrograde directions (n = 7), while the continuous line indicates a period of no-flow conditions interposed between the orthograde and retrograde flows (n = 6).) All parameters are normalized to the 0 cmH₂O pressure gradient condition.