Fig. 4.

SM-21, a specific antagonist of the σ₂-receptor, did not block the effects of afobazole (Afob). A: representative trace of an isolated rat mesenteric lymphatic pumping in the presence of SM-21 (2 μM) and afobazole (50 and 100 μM). Lymphatics frequently stopped pumping with 100 µM afobazole in the presence of SM-21, so only 50 and 100 µM afobazole were used for analysis. B–G: summarized data (means ± SE) from 4 isolated lymphatic vessels, each from a different rat. Data represent average values of each parameter obtained during the last 2 min of baseline and SM-21 periods and a 2-min period during each afobazole concentration starting 4 min after administration of afobazole. Mean values shown for the 100 µM afobazole groups include lymphatics that stopped pumping. B and C: application of 100 µM afobazole in the presence of SM-21 caused a significant decrease in contraction frequency (CF) and no change in end-diastolic diameter (EDD) normalized to maximal passive diameter (MaxD). D: 50 and 100 μM afobazole significantly elevated end-systolic diameter (ESD) normalized to MaxD (ESD/MaxD) in the presence of SM-21 compared with SM-21 alone. For lymphatics that stopped pumping, diameter/MaxD was used for the ESD/MaxD calculations. E–G: in the presence of SM-21 and compared with SM-21 alone, 100 µM afobazole significantly decreased amplitude of contraction normalized to MaxD (AMP/MaxD), ejection fraction (EF), and fractional pump flow (FPF). For lymphatics that stopped pumping, the value for these parameters was zero. Data were analyzed by repeated-measures ANOVA with the Geisser-Greenhouse correction; when this test identified a significant trend, multiple comparisons were performed using Dunnett’s test with the inhibitor alone as the control.