249. BKCa channels; a new target to treat maternal hypertension?

Abstract

Introduction Severe hypertension is a common indication for delivery amongst women with pre-eclampsia (PE), contributing to iatrogenic prematurity and its associated complications. Large-conductance calcium-activated potassium channels (BKCa), which promote vasorelaxation, are downstream targets of many vasoactive agents, including nitric oxide and angiotensin II. Estrogen-mediated increases in uterine artery BKCa activity are an important physiological adaptation to normal pregnancy. However, the role of BKCa has not been assessed in the wider systemic vasculature in either normal pregnancy or pregnancy pathologies. Outwith pregnancy, BKCa activity is reduced in association with PE risk factors, including age, hypoxia and diabetes. Furthermore, 5,6-EET, a BKCa inhibitor, is reported to be increased in the serum of women with PE. Objectives To determine the effect of BKCa activation on systemic resistance arteries of pregnant women and whether this is different in PE. Methods Resistance arteries ( Results NS11021 induced a substantial relaxation of omental resistance arteries obtained from women with either NP (N0; final relaxation Control 23 ± 8% Vs. NS11021 76 ± 4%; p Discussion Systemic arteries from women with both NP and PE relax in response to activation of BKCa channels. Direct BKCa activation provides an opportunity to bypass the inherent vascular dysfunction of PE to achieve comparable vasorelaxation in women with PE. On-going work will determine whether BKCa-activating compounds can offer a new treatment for maternal hypertension in PE.