Hypoxia Induces Aortic Hypertrophic Growth, Left Ventricular Dysfunction, and Sympathetic Hyperinnervation of Peripheral Arteries in the Chick Embryo

Abstract

Background-Low birth weight is associated with an increased incidence of cardiovascular diseases, including hypertension, later in life. This suggests that antenatal insults program for fetal adaptations of the circulatory system. In the present study, we evaluated the effects of mild hypoxia on cardiac function, blood pressure control, and arterial structure and function in near-term chick embryos. Methods and Results-Chick embryos were incubated under normoxic (21% O 2 ) or hypoxic (15% O 2 ) conditions and evaluated at incubation day 19 by use of histological techniques, isolated heart preparations, and in vivo measurements of sympathetic arterial tone and systemic hemodynamics. Chronic hypoxia caused a 33% increase in mortality and an 11% reduction in body weight in surviving embryos. The lumen of the ascending aorta in hypoxic embryos was 23% smaller. Left ventricular systolic pressure was 22% lower, and heart weight/body weight ratio was 14% higher. In resistance arteries of hypoxic embryos, in vivo baseline tone was 23% higher, norepinephrine sensitivity was similar, and norepinephrine release from sympathetic nerves increased 2-fold, indicating sympathetic hyperinnervation. Mean arterial pressure and heart rate were similar under resting conditions, but chronically hypoxic embryos failed to maintain blood pressure during acute stress. Conclusions-This study indicates that mild hypoxia during embryonic development induces alterations in cardiac and vascular function and structure and affects hemodynamic regulation. These findings reveal that antenatal insults have profound effects on the control and design of the circulatory system that are already established at birth and may program for hypertension and heart failure at a later age.

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

“…Hypoxia is a physiologic stimulus for vasculogenesis in development and pathology (Rouwet et al, 2002;Chan and Burggren, 2005). On the tissue level, hypoxia stimulates VEGF production via hypoxia-inducible factor (HIF) (Forsythe et al, 1996).…”

“…From those, one of the most pronounced epigenetic factors influencing vasculogenesis is hypoxia (Ribatti, 2006). Effects of hypoxia on cardiac development were studied for some time (Jaffee, 1978;Rouwet et al, 2002;Sharma et al, 2006). Recently, regional differences in myocardial tissue oxygenation during development were described (Wikenheiser et al, 2006), and regions with the lowest oxygen availability in the myocardium of the atria and interventricular septum were correlated with known sites of formation of coronary vessel and pacemaking and conduction system.…”

Effect of chronic hypoxia during embryonic development on physiological functioning and on hatching and post-hatching parameters related to ascites syndrome in broiler chickens

“…The significantly higher plasma lactic acid levels in embryos incubated at high altitude compared with embryos incubated at low altitude demonstrate anaerobic metabolism as a consequence of the hypoxic conditions at high altitude (Hassanzadeh et al, 1997). Rouwet et al (2002) demonstrated that chronic hypoxia during embryonic development induces structural and functional cardiovascular abnormalities (e.g. left ventricular dysfunction) in the nearterm chick embryos.…”

Renal Denervation Abolishes Hypertension in Low-Birth-Weight Offspring From Pregnant Rats With Reduced Uterine Perfusion

“…21 Additionally, hypoxia during fetal development leads to increased sympathetic innervation. 22,23 However, no further assessment of the SNS in association with IUGR has been examined.Nutrient and oxygen supply limitations are the components of the intrauterine environment that limit fetal growth and result in small-for-gestational-age newborns. Because IUGR within the Western world is more likely the result of reduced uterine perfusion, 24 we have developed a model of fetal programming induced by placental insufficiency caused by hypoxia and fetal undernutrition.…”

“…21 Additionally, hypoxia during fetal development leads to increased sympathetic innervation. 22,23 However, no further assessment of the SNS in association with IUGR has been examined.…”