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

Abstract.

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 (E _max). Bisexual infection increased the E _max 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 E _max (1.03±0.2 mN.s) in relation to non-infected control animals (E _max = 0.54±0.08 mN.s). Sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA) inhibition with 100 nM thapsigargin reduced the E _max 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 (Cl_Ca) with 10 µM niflumic acid reduced the E _max 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 E _max of two vasoconstrictors, possibly by increasing membrane depolarisation through a more effective opening of Cl_Ca channels, with calcium entering through L-type Ca²⁺ channels.