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 ( 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 Ca(2+)-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 Ca(2+) channels (L-type) was higher in portal veins from infected than non-infected control mice. Inhibition of Ca(2+)-activated chloride channels (Cl(Ca)) with 10 micro M 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 Ca(2+) channels.
Silva
C L M
CL
Laboratório de Farmacologia Bioquímica e Molecular, Departamento de Farmacologia Básica e Clínica, ICB, Universidade Federal do Rio de Janeiro, RJ, Brazil.
Lenzi
H L
HL
Silva
V F M
VF
Paulo
F O
FO
Noël
F
F
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D011169:Portal Vein / Q000166:cytology / Q000473:pathology / Q000503:physiopathology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012550:Schistosoma mansoni / Q000472:pathogenicity*; D012555:Schistosomiasis mansoni / Q000378:metabolism / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D012701:Serotonin / Q000494:pharmacology; D012737:Sex Factors; D012908:Snails; D014661:Vasoconstriction
D012701:Serotonin; D000109:Acetylcholine; D002118:Calcium