Fig. 2.

BD 1047, a specific antagonist of the σ₁-receptor, reduced effects of afobazole (Afob) on lymphatic contractions. A: representative trace of vessel diameter as a function of time during baseline, in the presence of BD 1047 (200 nM), and after subsequent addition of 50, 100, and 150 μM afobazole. B–G: summarized data (means ± SE) from 7 isolated lymphatic vessels, each from a different rat. Data represent average values of each parameter obtained during the last 2 min of the baseline and BD 1047 periods and a 2-min period during each afobazole concentration starting 4 min after administration of afobazole. B: pretreatment with BD 1047 followed by afobazole caused an apparent trend in contraction frequency (CF) that was significant (P = 0.0266) when tested by repeated-measures ANOVA. However, multiple comparisons with Dunnett’s test revealed no significant differences between BD 1047 treatment alone and the time points after which afobazole was administered. C: in the presence of BD 1047, treatment with 100 µM (but not 50 or 150 µM) afobazole caused a significant increase in end-diastolic diameter (EDD) normalized to maximal passive diameter (MaxD; 0.891 ± 0.010 in the presence of BD 1047 alone vs. 0.9267 ± 0.018 in the presence of BD 1047 + 100 µM afobazole, mean ± SE, P = 0.0183). D: only 150 µM afobazole caused a significant increase in end-systolic diameter (ESD) normalized to MaxD (ESD/MaxD) in the presence of BD 1047. E–G: only 150 µM afobazole caused a significant decrease in amplitude of contraction (AMP) normalized to MaxD (AMP/MaxD), ejection fraction (EF), and fractional pump flow (FPF) in the presence of BD 1047. 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.