REGULATION OF THE VASOMOTOR ACTIVITY OF LYMPH MICROVESSELS BY NITRIC-OXIDE AND PROSTAGLANDINS

It was shown previously that the presence of endothelium modulates spo ntaneous vasomotion of small lymphatic vessels. In the present study, we aimed to elucidate the nature of endothelium-derived factors, produ ced in basal conditions and in response to agonists, that affect the s mooth muscle tone of lymph microvessels in vitro. Afferent lymph micro vessels were isolated from rat iliac lymph nodes, cannulated with glas s micropipettes, and pressurized (6 cmH(2)O), and changes in their dia meter were investigated with video microscopy. In resting conditions, isolated lymph vessels exhibited spontaneous constrictions and dilatio ns. 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) t o 10(-5) M) and sodium nitroprusside (SNP, 10(-8) to 10(-6) M) tempora rily abolished diameter oscillations, increasing the diameter of lymph atics dose dependently. For example, 10(-5) M ACh and 10(-6) M SNP inc reased the diameter (D-max) by 15.2 +/- 2.2 and 25.0 +/- 2.7 mu m, res pectively. Treatment of vessels with N-G-nitro-L-arginine (10(-4) M) s ignificantly reduced the amplitude of diameter oscillations and nearly completely eliminated ACh-induced dilation of lymph microvessels, whe reas 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) d ilated (up to 40 mu m), lymphatic vessels. Indomethacin (10(-5) M) inc reased both D-max and D-min, and completely inhibited AA-induced const rictions, but did not affect PGE(2)-induced dilations of lymph microve ssels. AA-induced constrictions of lymphatics were converted into dila tions 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)-indu ced dilations were not affected. We conclude that endothelial nitric o xide and prostaglandins are important modulators of lymphatic vasomoti on, hence pumping activity of lymph microvessels in vivo.