As noted irst from animal studies, uterine contractions, either spontaneous or induced, lower uterine blood flow proportionally to contraction intensity (Assali, 1968). A tetanic contraction yields a precipitous fall in uterine blood flow. In humans, three-dimensional power Doppler angiography has also demonstrated reduced uterine blood low during contractions Gones, 2009). Using a similar technique, resistance to blood low in both maternal and fetal vessels was found to be greater during the second stage of labor compared with the first (Baron, 2015). Given that baseline uterine blood low is diminished in pregnancies complicated by fetal-growth restriction, these fetuses may tolerate spontaneous labor less efectively (Ferrazzi, 2011; Simeone, 2017).
The vessels that supply the uterine corpus widen and elongate yet preserve their contractile function (Mandala, 2012). In contrast, the spiral arteries, which directly supply the placenta, vasodilate but completely lose contractility. This presumably results from endovascular trophoblast invasion that destroys the intramural muscular elements (Chap. 5, p. 91). It is this vasodilation that allows maternal-placental blood low to progressively rise during gestation. Given that blood flow increases proportionally to the fourth power of the radius of the vessel, small increases in vessel diameter result in tremendous augmentation of uterine artery blood low. For example, in one study, the uterine artery diameter grew from only 3.3 mm to 3.7 mm between 22 and 29 weeks' gestation, but mean velocity increased 50 percent, from 29 to 43 cm/sec (Flo, 2010).
The downstream fall in vascular resistance is another key factor that accelerates low velocity and shear stress in upstream vessels. In turn, shear stress leads to circumferential vessel growth. Nitric oxide-a potent vasodilator-appears to play a central role in regulating this process and is discussed later (p. 63). Indeed, endothelial shear stress and several hormones and growth facrors all augment endorhelial nitric oxide synthase (eNOS) and nitric oxide producrion (Crummer, 2009; Lim, 2015; Mandala, 2012; Pang, 2015). Facrors include estrogen, progesterone, activin, placental growth facror (PIG F), and vas cular endorhelial growrh factor (VEGF), which is a promoter of angiogenesis. As an impo((am aside, VEGF and PIGF signaling is attenuated in response to excess placenral secretion of their soluble recepror-soluble FMS-like yrosille kinase I (sFlt-I). An ing PIGF and VEGF concentrations and is importanr in pre eclampsia parhogenesis (Chap. 40, p. 716).
Normal pregnancy is also characterized by vascular refrac mriness CO the pressor efects of infused angiotensin II, and rhis raises ureropiacenral blood Aow (Rosenfeld, 1981,e2012).
relaxin and certain adipocyrokines (Vodsrrcil, 201e2). Chemeri1 is an adipocycokine secreted by several rissues, including the placenra (Garces, 2013; Kasher-Meron, 2014). Irs concentra tion rises as gestadon advances and serves ro increase human umbilical eNOS activity, which mediates greater blood Aow (Wang, 2015). Anorher adipocyrokine-viotil-raises VEGF cells derived from the placemal amnion (Astern, 2013). Orher adipocyrokines include lepfin, resistin, and 1diponectin, which (Pole', 2014).