Effects of perinatal exposure to hypoxia upon the pulmonary circulation of the adult rat.
The hypothesis on Fetal and Infant Origins of Adult Disease proposes that an altered in utero environment may impair fetal development and physiological function, increasing susceptibility to disease in adulthood. Previous studies demonstrated that reduced fetal growth predisposes to adult cardiovascular diseases. Maternal smoking and high altitude are also linked to reduced fetal growth and adult disease, and both cause fetal hypoxia. We therefore wanted to determine whether fetal hypoxia produces alterations in the adult pulmonary vasculature. Body and ventricular weight, pulmonary arterial compliance and vasoreactivity to potassium chloride (KCl), prostaglandin F2alpha (PGF2alpha), acetylcholine (ACh) and sodium nitroprusside (SNP) were studied in adult rats exposed to 10 % hypoxia throughout the perinatal period, compared to age-matched controls. Rats exposed to perinatal hypoxia had reduced body weight (199+/-15 vs. 294+/-10 g, P<0.001), elevated right ventricular weight (70.3+/-8.8 vs. 51.4+/-1.2 mg/100 g, P<0.05), elevated left ventricular weight (281+/-27 vs. 232+/-5 mg/100 g, P<0.05), reduced pulmonary arterial compliance (35.2+/-2.0 vs. 46.4+/-2.4 microm/mN, P<0.05) and reduced maximal pulmonary vasoconstriction to KCl (1.74+/-0.14 vs. 2.63+/-0.31 mN/mm, P<0.01), and PGF2(2alpha) (1.40+/-0.14 vs. 2.47+/-0.44 mN/mm, P<0.05). Perinatal exposure to hypoxia had a profound effect upon the adult pulmonary circulation, which could predispose to cardiopulmonary diseases in adulthood.
Section of Respiratory medicine, Division of Academic Medicine, University of Hull, Castle Hill Hospital, Cottingham, United Kingdom. R.D.Jones@sheffield.ac.uk
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Morice
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Emery
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003187:Compliance; D005260:Female; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011651:Pulmonary Artery / Q000002:abnormalities* / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar