Background: Our objective was to investigate the role of hydrogen peroxide in the vasocontraction induced in the human umbilical artery by serotonin.
Methods: Umbilical arteries collected from healthy women at term were cut helically and suspended in an organ bath to record isometric mechanical activity. In Study I, we measured the concentration-contraction response to serotonin with or without pretreatment with hydrogen peroxide (0.01-10 microM). In Study 2, vessels were pre-incubated with L-arginine (0.1-10mM), or with hydrogen peroxide (10 mM) and L-arginine (1 mM), then serotonin was added cumulatively. In Study 3, vessels were suspended in a calcium-free solution containing potassium chloride 20 mM, and a cumulative concentration-response curve to calcium chloride (10(-5)-10(-3) M) was constructed for vessels pretreated with hydrogen peroxide (10 microM). In Study 4, vessels were pre-treated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and hydrogen peroxide (10 microM), and then prostaglandin F2 alpha (9.0 x 10(-7) M). Finally, we measured the 5-HT1 receptor-mediated relaxation induced by serotonin.
Results: Hydrogen peroxide (1 or 10 microM) significantly potentiated the contractile response to serotonin (p < 0.04, p < 0.005). L-arginine (1 or 10 mM) significantly reduced the contractile response to serotonin (p < 0.02, p < 0.0002). Pretreatment with L-arginine significantly suppressed the potentiating effect of hydrogen peroxide on the serotonin-induced contraction. The sensitivity of the arteries to calcium chloride in the presence of hydrogen peroxide did not differ from that in the control group. Pretreatment with hydrogen peroxide significantly reduced the 5-HT1 serotoninergic receptor-mediated relaxation at higher concentrations of serotonin (1.23 x 10(-4) M, 2.47 x 10(-4) M, 2.47 x 10(-4) M).
Conclusion: Hydrogen peroxide potentiated the umbilical artery contraction induced by serotonin. This action may be mediated by suppression of endogenous nitric oxide activity.