Long-lasting adverse effects of prenatal hypoxia on developing autonomic nervous system and cardiovascular parameters in rats.
To determine whether prenatal hypoxia increases the risk of developing cardiovascular disorders as an adult and, if so, the identity of the cell mechanisms involved in such dysfunction, we evaluated the sympathoadrenal system and central areas related to cardiovascular events during development and the cardiovascular parameters in adults. Pregnant rats were exposed to hypoxia (10% oxygen) from embryonic day (E) 5 to E20 and the offspring studied at 1, 3, 9 and 12 weeks of age for neurochemistry and at 12 weeks of age for cardiovascular analysis. In the 1-, 3- and 9-week-old offspring, the levels and utilization of catecholamines were reduced in sympathetic ganglia, in target organs, in adrenals and in the rostral part of the A2 cell group in the nucleus tractus solitarius, but were increased in the locus coeruleus. In the 12-week-old adult offspring, the lowered autonomic nervous activity was restricted to cardiac-related structures, i.e. the stellate ganglion, heart and adrenals. In adult rats, prenatal hypoxia did not affect the cardiac parameters under resting conditions but increased blood pressure and the variability of blood pressure and heart rate under stress conditions. The altered metabolic activity of the sympathoadrenal system and related central areas during development and at adulthood for most structures might be part of the potential mechanisms contributing to cardiovascular disorders in adults.
Peyronnet
Julie
J
Department of Woman and Child Health, Karolinska Institute, 171 76 Stockholm, Sweden. julie@child.ks.se
Dalmaz
Yvette
Y
Ehrström
Marcus
M
Mamet
Julie
J
Roux
Jean-Christophe
JC
Pequignot
Jean-Marc
JM
Thorén
H Peter
HP
Lagercrantz
Hugo
H
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000196:embryology* / Q000378:metabolism; D005260:Female; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013233:Stellate Ganglion / Q000196:embryology* / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology
D010100:Oxygen; D009638:Norepinephrine