Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins

It was shown previously that the presence of endothelium modulates spontaneous vasomotion of small lymphatic vessels. In the present study, we aimed to elucidate the nature of endothelium-derived factors, produced in basal conditions and in response to agonists, that affect the smooth muscle tone of lymph microvessels in vitro. Afferent lymph microvessels were isolated from rat iliac lymph nodes, cannulated with glass micropipettes, and pressurized (6 cmH(2)O), and changes in their diameter were investigated with video microscopy. In resting conditions, isolated lymph vessels exhibited spontaneous constrictions and dilations. The maximum and minimum diameters (D(max) and D(min)) were 149.8 +/- 2.9 and 85.8 +/- 3.6 mu m, respectively. Acetylcholine (ACh, 10(-7) to 10(-5) M) and sodium nitroprusside (SNP, 10(-8) to 10(-6) M) temporarily abolished diameter oscillations, increasing the diameter of lymphatics dose dependently. For example, 10(-5) M ACh and 10(-6) M SNP increased the diameter (D(max)) by 15.2 +/- 2.2 and 25.0 +/- 2.7 mu m, respectively. Treatment of vessels with N(G)-nitro-L-arginine (10(-4) M) significantly reduced the amplitude of diameter oscillations and nearly completely eliminated ACh-induced dilation of lymph microvessels, whereas SNP (10(-6) M) elicited a significantly greater dilation (55.6 +/- 7.5 mu m). Arachidonic acid (AA, 10(-8) to 10(-6) M) constricted (up to 50 mu m), whereas prostaglandin E(2) (PGE(2), 10(-9) to 10(-7) M) dilated (up to 40 mu m), lymphatic vessels. Indomethacin (10(-5) M) increased both D(max) and D(min), and completely inhibited AA-induced constrictions, but did not affect PGE(2)-induced dilations of lymph microvessels. AA-induced constrictions of lymphatics were converted into dilations after treatment with SQ-29,548, a selective PGH(2)-thromboxane A(2) (PGH(2)-TxA(2), 10(-6) M) receptor antagonist, whereas PGE(2)-induced dilations were not affected. We conclude that endothelial nitric oxide and prostaglandins are important modulators of lymphatic vasomotion, hence pumping activity of lymph microvessels in vivo.