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

Background. We have demonstrated that hydrogen peroxide (H 2 O 2 ) 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 H 2 O 2 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 F 2 α (9X10 −7 M) were measured (isometric mechanical activity). Segments were treated with H 2 O 2 (10 −6 ∼ 10 −4 M) alone or H 2 O 2 after pretreatment with a scavenger of hydroxyl radicals (mannitol, 10 −2 M), an inhibitor of PKC (H‐7, 6X10 −7 M). Effect of an activator of PKC (12‐tetradecanoyl phorbol‐13 acetate, TPA, 10 −6 M) on PG F 2 α‐induced tension was determined. Effects of H 2 O 2 (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 H 2 O 2 in a concentration‐dependent manner. Pretreatment with mannitol significantly suppressed the vasospastic effect of H 2 O 2 . Pretreatment with H‐7 did not alter the response to H 2 O 2 . TPA did not produce a significant change in PG F 2 α‐induced tension. Pretreatment with H 2 O 2 (10 −5 M) did not alter the contractile response to external calcium. Conclusion. H 2 O 2 potentiated vascular tension in human umbilical arteries, a process that is independent of PKC and the voltage‐dependent calcium channel. The vasospastic effect of H 2 O 2 may be mediated by a suppression of the activity of nitric oxide and prostacyclin.