Flow reduces the amplitude and increases the frequency of lymphatic vasomotion: role of endothelial prostanoids

Fluid dynamic forces have substantial effects on the movement of lymph and activity of lymph vessels. The effect of increases in intraluminal flow on spontaneous pumping activity of isolated collecting lymphatics has not yet been characterized in a condition in which the intraluminal pressure is con stant. Thus, in afferent lymph microvessels isolated from rat iliac lymph n odes, changes in maximum (D-max) and minimum (D-min) diameter to increases in perfusate flow were investigated in the presence of a constant perfusion pressure of 6 cmH(2)O. Intraluminal flow was elicited by increases in the difference between outflow and inflow pressures (P-diff, from 0 to 6 cmH(2) O). Diameters were measured by videomicroscopy, In response to increases in perfusate flow, D-max and D-min, of lymphatics decreased from 157.5 +/- 6. 1 to 90.9 +/- 5.6 mu m and from 91.9 +/- 5.3 to 66.3 +/- 3.6 pm, respective ly, whereas vasomotion frequency increased from 18.0 +/- 0.7 min(-1) to 23. 4 +/- 1.1 min(-1) (at P-diff of 4 cmH(2)O). Removal of extracellular Ca2+ a bolished spontaneous diameter oscillations; under these conditions the pass ive diameter of lymphatics was 216.0 +/- 7.1 mu m and did not change in res ponse to increases in perfusion. In the absence of endothelium, flow-induce d changes in D-max, D-min, and oscillation frequency were eliminated. N-ome ga-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, di d not affect flow-induced changes in diameter of lymphatics. In contrast, i ndomethacin, an inhibitor of prostaglandin synthesis, or SQ-29,548, a PGH(2 )/thromboxane A(2) (PGH(2)/TxA(2)) receptor blocker, inhibited the perfusio n-induced reduction of D-max and D-min, of lymphatics and also the increase in the frequency of vasomotion. These findings suggest that the sensitivit y of lymphatic endothelium to increases in intraluminal flow could provide an important local intrinsic mechanism for the control of lymphatic resista nce by release of constrictor prostanoids PGH(2)/TxA(2).