Effects of superoxide and peroxynitrite on vascular tension in the human umbilical artery

While nitric oxide (NO) has been demonstrated to regulate vascular tone, superoxide (O2-) may also have an important role in regulating tension in the human fetoplacental vasculature. We therefore evaluate the effects of O2- and peroxynitrite (ONOO-) on vascular tension in isolated human umbilical arteries.

Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium chloride (KCl)-induced tension were measured in umbilical artery segments with intact endothelium.

We found that hypoxanthine plus xanthine oxidase significantly potentiated vascular tension, and that this effect was suppressed by pretreatment with L(NG)-monomethyl arginine (LNMA). Pretreatment with hypoxanthine plus xanthine oxidase, however, significantly inhibited the relaxation induced by the calcium ionophore A23187. 3-morpholinosydomine (SIN-1), which releases O2- and NO simultaneously produced a significant dose-dependent relaxation of vascular tension, which pretreatment with hemoglobin did not affect SIN-1-induced relaxation. Pretreatment with methylene blue significantly attenuated, while pretreatment with superoxide dismutase (SOD) significantly potentiated this effect.

These findings suggest that O2- potentiates vascular tension in human umbilical artery, in part, by suppressing NO synthesis in the endothelium. The vasorelaxation by exogenously generated ONOO suggests that this moiety has biological relevance in vasoregulation of the human umbilical artery.