Involvement of dysregulated IK and SK channels in preeclampsia.

INTRODUCTION

Excessive constriction of placental chorionic plate arteries (CPAs) may be associated with preeclampsia (PE). Nitric oxide (NO) as well as intermediate and small Ca-activated K channels (IK and SK) plays vital roles in vasodilation of CPAs. We hypothesized that dysregulated IK and SK channels may be involved in the pathogenesis of PE mediated by the impaired NO system on CPAs.

METHODS

The location of IK and SK channels, activities of NO synthases (NOS), and expression levels of these molecules were studied on CPAs from 30 normal pregnancies and 30 PE. The vasodilating function of CPAs was measured under openers or blockers of IK/SK channels in the presence or absence of NO donor or inhibitor.

RESULTS

IK and SK channels were located both on endothelium and on smooth muscles of CPAs and the expressions of them were downregulated in PE women comparing to those in normal pregnant women. The protein expressions of endothelial NOS (eNOS) and inducible NOS (iNOS) were downregulated on CPAs in PE accompanied by decreased activity of eNOS. Notably, the vasodilatory functions mediated by IK/SK channels and by NO were aberrant on preeclamptic CPAs. In addition, IK and SK channels were responsible for nitric oxide (NO)-attributable vasorelaxation and activity modulation of NO synthases.

CONCLUSIONS

This study provides evidence that dysregulated IK and SK channels might contribute to fetal pathogenesis of PE through direct promotion of vascular constriction of CPAs and through affecting functions of NO and activities of NOS.