Fig. 4.

Differential effects of selective inducible nitric oxide synthase (iNOS) inhibition vs. total nitric oxide synthase (NOS) inhibition on lymphatic vessel contractions and lymph drainage in tumor necrosis factor–transgenic (TNF-Tg) mice with flaring arthritis. TNF-Tg mice more than 5 months old with severe ankle arthritis were used. a TNF-Tg mice (n = 5) were subjected to real-time near-infrared indocyanine green (NIR-ICG) imaging to quantify the afferent lymphatic pulse before, during, and following a direct injection of saline (a, b) or L-N⁶-(1-iminoethyl)lysine 5-tetrazole-amide (L-NIL) (c, d) into the footpad. Representative NIR-ICG images illustrate the lack of ICG lymphatic drainage from the injection site in the footpad to the region of the popliteal lymph node at 1 h postinjection (a, c). No remarkable changes were observed 9 minutes after saline injection (b). However, ICG was detected in the primary lymphatic vessel (LV; arrow) and the popliteal lymph node (PLN; arrowhead) within 4 minutes after L-NIL injection (d). b The lymphatic vessel contraction frequency was determined by assessing pulses in the NIR-ICG signal intensity in the region of interest (red circles), which was graphed over time during the imaging session. Note the recovery of lymphatic pulses (red arrows) after the iNOS inhibitor L-NIL (green line) injection, while saline did not affect lymphatic contraction frequency (orange line). c TNF-Tg mice and their wild-type (WT) littermates (n = 4) underwent pre- and posttreatment NIR-ICG imaging to assess the effects of 6 weeks of saline, L-NIL, and N _ω-nitro-L-arginine methyl ester (l-NAME) on lymphatic vessel contractions (c) and percentage ICG clearance (d). Figure 4c, *P<0.05 between groups.  Figure 4d, *P<0.05 vs WT. #P<0.05 vs. TNF-Tg