Effect of gestational diabetes mellitus and pregnancy-induced hypertension on human umbilical vein smooth muscle KATP channels

Abstract

Gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) can jeopardize mother and/or fetus. Vascular ATP-sensitive potassium (K_ATP) channels most likely participate in the processes of diabetes and hypertension. The aim of this research was to examine whether GDM and PIH cause changes in the expression and function of K_ATP channels in vascular smooth muscle of human umbilical vein (HUV). Western blot and immunohistochemistry detected significantly decreased expression of Kir6.1 subunit of K_ATP channels in GDM and PIH, while the expression of SUR2B was unchanged. In GDM, a K⁺ channel opener, pinacidil caused reduced relaxation of the endothelium-denuded HUVs compared to normal pregnancy. However, its effects in HUVs from PIH subjects were similar to normal pregnancy. In all groups K_ATP channel blocker glibenclamide antagonized the relaxation of HUV induced by pinacidil without change in the maximal relaxations indicating additional K_ATP channel-independent mechanisms of pinacidil action. Iberiotoxin, a selective antagonist of large-conductance calcium-activated potassium channels, inhibited the relaxant effect of pinacidil in PIH, but not in normal pregnancy and GDM. Experiments performed in K⁺-rich solution confirmed the existence of K⁺-independent effects of pinacidil, which also appear to be impaired in GDM and PIH. Thus, the expression of K_ATP channels is decreased in GDM and PIH. In GDM, vasorelaxant response of HUV to pinacidil is reduced, while in PIH it remains unchanged. It is very likely that K_ATP channels modulation and more detailed insight in K_ATP channel-independent actions of pinacidil may be precious in the therapy of pathological pregnancies.

Keywords: Gestational diabetes mellitus (GDM); Human umbilical vein; K(ATP) channels; Pinacidil; Pregnancy-induced hypertension (PIH).