Chronic in ovo hypoxia decreases pulmonary arterial contractile reactivity and induces biventricular cardiac enlargement in the chicken embryo

Abstract

Although chronic prenatal hypoxia is considered a major cause of persistent pulmonary hypertension of the newborn, experimental studies have failed to consistently find pulmonary hypertensive changes after chronic intrauterine hypoxia. We hypothesized that chronic prenatal hypoxia induces changes in the pulmonary vasculature of the chicken embryo. We analyzed pulmonary arterial reactivity and structure and heart morphology of chicken embryos maintained from days 6 to 19 of the 21-day incubation period under normoxic (21% O(2)) or hypoxic (15% O(2)) conditions. Hypoxia increased mortality (0.46 vs. 0.14; P < 0.01) and reduced the body mass of the surviving 19-day embryos (22.4 +/- 0.5 vs. 26.6 +/- 0.7 g; P < 0.01). A decrease in the response of the pulmonary artery to KCl was observed in the 19-day hypoxic embryos. The contractile responses to endothelin-1, the thromboxane A(2) mimetic U-46619, norepinephrine, and electrical-field stimulation were also reduced in a proportion similar to that observed for KCl-induced contractions. In contrast, no hypoxia-induced decrease of response to vasoconstrictors was observed in externally pipped 21-day embryos (incubated under normoxia for the last 2 days). Relaxations induced by ACh, sodium nitroprusside, or forskolin were unaffected by chronic hypoxia in the pulmonary artery, but femoral artery segments of 19-day hypoxic embryos were significantly less sensitive to ACh than arteries of control embryos [pD(2) (= -log EC(50)): 6.51 +/- 0.1 vs. 7.05 +/- 0.1, P < 0.01]. Pulmonary vessel density, percent wall area, and periarterial sympathetic nerve density were not different between control and hypoxic embryos. In contrast, hypoxic hearts showed an increase in right and left ventricular wall area and thickness. We conclude that, in the chicken embryo, chronic moderate hypoxia during incubation transiently reduced pulmonary arterial contractile reactivity, impaired endothelium-dependent relaxation of femoral but not pulmonary arteries, and induced biventricular cardiac hypertrophy.

Impact of Hypoxia on Early Chick Embryo Growth and Cardiovascular Function

“…O xygen tension is a critical determinant of appropriate embryonic and fetal development (1)(2)(3)(4)(5)(6)(7), and hypoxia is associated with increased fetal mortality. Specifically, hypoxia is known to cause decreased birth weight, cerebrovascular anomalies, CV dysfunction, and altered angiogenesis (2-6), with hypoxia producing greater negative effects later in gestation (7).…”

“…Most studies of the detrimental effects of hypoxia on CV morphogenesis and function have focused on late gestation (6,19,20). The current study was designed to investigate the CV response to hypoxia during early embryogenesis and to test the hypothesis that hypoxia alters both embryonic ven-tricular and vascular function in the early embryo.…”

Development of a fast, objective, quantitative methodology to monitor angiogenesis in the chicken chorioallantoic membrane during development

“…Rahn et al (1979) demonstrate that, although the embryo grows, the oxygen uptake reaches a plateau from around ED 15 onwards until internal pipping. This may lead to hypoxic conditions and therefore a higher susceptibility to ascites by triggering structural changes in the heart (Decuypere et al, 2000;Villamor et al, 2004). Ascites is a syndrome related to cardiovascular and pulmonary ailments, and the main cause of non-infectious mortality in the broiler sector, leading to economic losses and animal welfare problems.…”

Effect of oxygen supplementation in a hatchery at high altitude and growth performance of broilers reared at low altitude

“…Growth increases the need for O 2 consumption (Beker et al, 2003), and rapidly growing broiler chickens need O 2 for their high metabolic requirements (Julian et al, 1989). As the O 2 level decreases with altitude, exposure to chronic hypoxia increases mortality during incubation and decreases growth as a result of adaptation (Julian, 2000;Villamor et al, 2004). The hypoxic condition during incubation decreases chick weight (Dzialowski et al, 2002;Sharma et al, 2006;Zhang et al, 2008).…”