Hypoxic fetoplacental vasoconstriction (HFPV) is proposed to direct fetal blood to O2-rich areas of the placenta to facilitate optimal transfer of O2 and nutrients to the developing fetus[1]. A similar process in lung, ventilation-perfusion matching, is achieved by hypoxic vasoconstriction and mediated by Kv1.5 inhibition, an O2-sensitive voltage-gated K+ channel[2]. O2-sensitive K+ channels have been implicated in HFPV[3] but their molecular identity remains unknown. HFPV has been demonstrated experimentally in response to acute O2 reductions over a range higher than the placenta encounters in vivo[1, 3]. Here we test the hypothesis that Kv1.5 contributes to agonist-induced chorionic plate artery constriction following acute and chronic exposures to pathophysiologically relevant O2 tensions. Chorionic plate arteries were dissected from normal term placentas (N=14), bathed in physiological salt solution (PSS) and immediately prepared for isometric tension studies. Vasoconstriction was assessed with U46619 (thromboxane-mimetic 10-10-2×10-6M) in the presence and absence of 4-aminopyridine (4-AP; 1mM) and DPO-1 (3µm), blockers of voltage-gated (Kv) and Kv1.5 channels respectively. These acute experiments were performed in 5% O2/ 5% CO2 (N=8; pO2=6%; normoxia) or 5% CO2 in N2 (N=6; pO2=2%; hypoxia) gassed PSS. Vessels from the same placentas were isolated and cultured for 48hr at 6% O2 (N=8) or 2% O2 (N=6) and experiments repeated to assess effects of chronic oxygenation. Significant differences (P<0.05) were assessed by Two-Way ANOVA and Mann-Whitney U Test. Chronic exposure/ culture at 6% and 2% O2 did not affect agonist-induced (U46619 dose-response curves) or depolarisation-induced (120mM KPSS) constrictions compared to acute exposure. Enhanced U46619 constriction was not observed following acute or chronic exposure to 2% O2 compared to 6% O2. In acute experiments, pre-incubation with 4-AP or DPO-1 caused a significant upward shift in the U46619 dose-response curve at 6% and 2% O2. However, this effect of Kv channel blockade on U46619-induced contraction was abolished in cultured vessels at either O2 tension compared to the respective time-matched controls. U46619-induced constriction of chorionic plate arteries was not increased in acute hypoxia or following culture in hypoxic conditions. In acute experiments, Kv and Kv1.5 channel inhibition increased U46619-induced constriction at both O2 tensions. Loss of Kv channel inhibition following culture at either O2 tension suggests Kv1.5 channel expression/function is not regulated by oxygenation over this range but may be an intrinsic characteristic of the culture process. In line with our previous reports of Kv1.5 expression in isolated smooth muscle cells[4], this study provides the first evidence for functional Kv1.5 channels in chorionic plate arteries over a pathophysiologically relevant oxygenation gradient for the placenta.