Cellular mechanisms involved in the increased contraction of portal veins from Schistosoma mansoni-infected mice

We previously reported that portal veins from mice infected with male Schistosoma mansoni exhibited an increased reactivity to 5-hydroxytryptamine (5-HT). Here, we extended our observations to mice infected by both male and female worms and we further investigated another constrictor agent and the mechanism(s) responsible for the enhanced maximal contraction (Emax). Bisexual infection increased the Emax of 5-HT (from 0.66±0.06 mN.s to 1.56±0.38 mN.s), in a similar way to the unisexual (male) infection. Infection with male worms increased portal vein reactivity to acetylcholine, as revealed by a higher Emax (1.03±0.2 mN.s) in relation to non-infected control animals (Emax = 0.54±0.08 mN.s). Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibition with 100 nM thapsigargin reduced the Emax of 5-HT by 35% in both tissues, discharging a deficiency of SERCA pump in infected animals. In contrast, the number of voltage-dependent Ca2+ channels (L-type) was higher in portal veins from infected than non-infected control mice. Inhibition of Ca2+-activated chloride channels (ClCa) with 10 µM niflumic acid reduced the Emax of 5-HT in portal veins more from infected than non-infected animals (remaining tension = 60.9±2.2% and 70.4±2.3%, respectively). Histopathological analysis revealed an increased content of collagen and elastin in portal veins from male S. mansoni-infected mice, compatible with an increased intraluminal pressure. In conclusion, male S. mansoni altered portal vein physiology, increasing the Emax of two vasoconstrictors, possibly by increasing membrane depolarisation through a more effective opening of ClCa channels, with calcium entering through L-type Ca2+ channels.