Maternal nutrient restriction during pregnancy impairs an EDHF‐like pathway in fetal coronary arteries without affecting large conductance, calcium‐activated K channel (BKCa) activity in smooth muscle cells

Abstract

We demonstrated previously that maternal nutrient restriction during pregnancy impairs an EDHF‐like pathway that is mediated via BKCa activation in fetal coronary arteries (CA). We now show that the impairment is not likely due to altered BKCa activity in CA smooth muscle cells. Pregnant ewes were fed a control or nutrient restricted diet from day 50–130 of gestation. In CA isolated from control fetal lambs, relaxation to bradykinin was partially inhibited by nitro‐l‐arginine (NLA). Iberiotoxin nearly abolished the NLA‐resistant response to bradykinin. In CA from undernourished animals, relaxation to bradykinin was fully suppressed by NLA. Whole‐cell BKCa currents were nearly identical in CA smooth muscle cells from control and nutrient restricted animals (peak current density= 46 ± 5 vs. 39 ± 6 pA/pF; n=6). 14,15‐EET (putative EDHF in CA) caused fetal CA relaxation and BKCa activation that was unaffected by maternal nutrient restriction. Similar results were obtained with the BKCa‐openers, BMS 191011 and NS 1619. Relaxation to bradykinin in fetal CA is mediated by NO, and by an EDHF‐like pathway that involves BKCa activation. Maternal undernutrition during pregnancy results in loss of the EDHF‐like pathway in fetal CA, an effect that is likely due to endothelial dysfunction (i.e. impaired synthesis and/or release of an EDHF‐like mediator) rather than impaired BKCa activity in CA smooth muscle cells. (NIH HD61532)