Published Online
on May 6, 2002

A more recent version of this article appeared on June 11, 2002

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Submitted on December 28, 2001
Revised on March 20, 2002
Accepted on March 21, 2002

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

E. V. Rouwet MD, PhD, A. N. Tintu MSc, M. W.M. Schellings MSc, M. van Bilsen PhD, E. Lutgens MD, PhD, L. Hofstra MD, PhD, D. W. Slaaf PhD, G. Ramsay MD, PhD, and F. A.C. le Noble PhD^*

From the Departments of Surgery (E.V.R., G.R.), Pathology (E.L.), and Cardiology (L.H.), University Hospital, and the Departments of Physiology (A.N.T., M.W.M.S., M.v.B., F.A.C.l.N.) and Biophysics (D.W.S.), Cardiovascular Research Institute, Maastricht, Netherlands.

^* To whom correspondence should be addressed. E-mail: flenoble{at}hotmail.com.

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% O₂) or hypoxic (15% O₂) 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.

Key words: hypoxia • hypertension • nervous system, sympathetic • heart defects, congenital

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