Vasospastic action of hydrogen peroxide in human umbilical artery: relation to protein kinase C and calcium influx.

BACKGROUND

We have demonstrated that hydrogen peroxide (H2O2) potentiated vascular tension in human umbilical artery, perhaps by suppressing the synthesis of nitric oxide and prostacyclin. This study was conducted to evaluate whether the activation of protein kinase C (PKC) or voltage-dependent calcium channel mediated the vasospastic effect of H2O2.

METHODS

Helical sections of the umbilical artery were obtained from healthy pregnant women who delivered between 37th and 39th week of gestation. Changes in the maximal tension induced by prostaglandin F2 alpha (9 x 10(-7) M) were measured (isometric mechanical activity). Segments were treated with H2O2 (10(-6)-10(-4) M) alone or H2O2 after pretreatment with a scavenger of hydroxyl radicals (mannitol, 10(-2) M), an inhibitor of PKC (H-7, 6 x 10(-7) M). Effect of an activator of PKC (12-tetradecanoyl phorbol-13 acetate, TPA, 10(-6) M) on PG F2 alpha-induced tension was determined. Effects of H2O2 (10(-5) M) on the response of umbilical artery segments to an external calcium (10(-6)-10(-3) M) were determined.

RESULTS

Vascular tension was potentiated by H2O2 in a concentration-dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H2O2. Pretreatment with H-7 did not alter the response to H2O2. TPA did not produce a significant change in PG F2 alpha-induced tension. Pretreatment with H2O2 (10(-5) M) did not alter the contractile response to external calcium.

CONCLUSION

H2O2 potentiated vascular tension in human umbilical arteries, a process that is independent of PKC and the voltage-dependent calcium channel. The vasospastic effect of H2O2 may be mediated by a suppression of the activity of nitric oxide and prostacyclin.