Fig. 3.

BD 1063, a specific σ₁-receptor antagonist, reduced effects of afobazole (Afob) on lymphatic contraction. A: representative trace of pumping of an isolated, cannulated rat mesenteric lymphatic vessel during baseline, in the presence of BD 1063 (200 nM), and after subsequent addition of 50, 100, and 150 μM afobazole. 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 the baseline and BD 1063 periods and a 2-min period during each afobazole concentration starting 4 min after administration of afobazole. B and C: in the presence of BD 1063, afobazole (50–150 µM) caused no significant trend in contraction frequency (CF; P = 0.2752) or end-diastolic diameter (EDD) normalized to maximal passive diameter (MaxD; P = 0.3963) as determined by repeated-measures ANOVA. D: only 100 µM afobazole caused a significant increase in end-systolic diameter (ESD) normalized to MaxD (ESD/MaxD) in the presence of BD 1063 compared with BD 1063 alone. Treatment with 150 µM afobazole, despite achieving a higher mean than 100 µM afobazole treatment, showed more variability, and compared with BD 1063 alone, produced a P value that was not considered significant. E: only 100 and 150 µM afobazole in the presence of BD 1063 significantly reduced amplitude of contraction (AMP) normalized to MaxD (AMP/MaxD) compared with BD 1063 alone. F: only 100 µM afobazole in the presence of BD 1063 significantly reduced ejection fraction (EF) compared with BD 1063 alone. Despite a lower mean EF, 150 µM afobazole in this case had a greater variance and, compared with BD 1063 alone, produced a P value that was not considered significant. G: no significant changes in fractional pump flow (FPF) were apparent when afobazole was applied at 50–150 µM in the presence of BD 1063 (P = 0.2492, repeated-measures ANOVA). 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.