This is surprising given that the placenta forms a crucial link between mother and her developing baby. This review will firstly describe our current understanding of how small fetoplacental blood vessels are affected by oxygenation. Secondly, the expression and function of K+ channels GW-572016 in vivo in small fetoplacental blood vessels will be discussed and the possible role of ambient oxygenation highlighted. Measurements of umbilical arterial (16–28 mmHg) and venous (28–35 mmHg; [40, 51]) blood samples suggest that human fetoplacental blood vessels experience oxygenation levels at term similar to those recorded in the IVS (40–45 mmHg; [30,
31, 6, 60]); i.e., a relatively hypoxic environment. Data using the perfused placental cotyledon model suggest that fetoplacental blood vessels can respond to local ambient oxygen [25, 28, 8, 27]; reducing perfusate
oxygenation increased pressure within the vascular circuit suggesting vascular contraction. However, one must question the physiological relevance of this data as oxygenation levels were reduced from “normoxia” of 400–500 mmHg down to 20–50 mmHg “hypoxia” [28, 8, 27, 55]. Data from Hampl et al. demonstrated reproducible HFPV and suggested that oxygen-sensitive K+ channels may be important for the detection and response to the hypoxic stimulus (see below for more detail) . However, oxygen levels in this study were manipulated from ~120 to ~60 mmHg high throughput screening compounds in large diameter placental vessels, conditions more akin to the “pulmonary” physiological range (140–20 mmHg) [41, 75, 57, 56]. Ramasubramanian et al. also noted an HFPV response and additionally suggested this was graded depending on the level of hypoxia ; however, these comparisons were made relative to the control oxygenation (140 mmHg) with only a minor differential noted across the likely physiological range (75 ± 3 mmHg peak fetal arterial pressure at 35 mmHg O2 vs. 78 ± 6 mmHg peak fetal arterial pressure at 0 mmHg O2). Data from Pierce et al. have suggested dilatation to hypoxia, not an HFPV effect ; perfusion
IKBKE of 25 mmHg O2 in fetal vs. 60 mmHg O2 in maternal perfusate stimulated a significant dilatation of perfused placental cotyledons compared with control data. Most recently, placental perfusion studies to assess hypoxic effects on placental metabolism, such as those of Soydemir et al., have utilized more appropriate conditions. However, significant changes in metabolic markers following the hypoxic challenge were not mirrored by alterations in perfusion pressure . Taken together, it is clear that the existence of a physiologically relevant HFPV response in human placenta still requires definitive proof; i.e., increased vascular tone in response to a hypoxic challenge from a physiologically relevant control oxygenation. Isolated fetoplacental blood vessel studies have also failed to demonstrate consistent effects of oxygenation.