Adult animals that have been perinatally exposed to
oxygen-rich atmospheres (
hyperoxia), recalling those used for
oxygen therapy in infants, exhibit a loss of hypoxic pulmonary vasoconstriction, whereas vasoconstriction elicited by depolarizing agents is maintained. Loss of pulmonary hypoxic vasoconstriction is not linked to alterations in
oxygen-sensitive K(+) currents in pulmonary artery smooth muscle cells. Loss of hypoxic vasoconstriction is associated with early postnatal oxidative damage and corrected by an
antioxidant diet. Perinatal
hyperoxia damages carotid body chemoreceptor cell function and the
antioxidant diet does not reverse it. The
hypoxia-elicited increase in
erythropoietin plasma levels is not affected by perinatal
hyperoxia. The potential clinical significance of the findings in clinical situations such as
pneumonia,
chronic obstructive pulmonary disease or general anaesthesia is considered.
ABSTRACT: Adult mammalians possess three cell systems that are activated by acute bodily
hypoxia: pulmonary artery smooth muscle cells (PASMC), carotid body chemoreceptor cells (
CBCC) and
erythropoietin (EPO)-producing cells. In rats, chronic perinatal
hyperoxia causes permanent carotid body (CB)
atrophy and functional alterations of surviving
CBCC. There are no studies on PASMC or EPO-producing cells. Our aim is to define possible long-lasting functional changes in PASMC or EPO-producing cells (measured as EPO plasma levels) and, further, to analyse
CBCC functional alterations. We used 3- to 4-month-old rats born and reared in a normal atmosphere or exposed to perinatal
hyperoxia (55-60% O2 for the last 5-6 days of pregnancy and 4 weeks after birth). Perinatal
hyperoxia causes an almost complete loss of hypoxic pulmonary vasoconstriction (HPV), which was correlated with lung oxidative status in early postnatal life and prevented by
antioxidant supplementation in the diet. O2 -sensitivity of K(+) currents in the PASMC of hyperoxic animals is normal, indicating that their inhibition is not sufficient to trigger HPV. Perinatal
hyperoxia also abrogated responses elicited by
hypoxia on
catecholamine and cAMP metabolism in the CB. An increase in EPO plasma levels elicited by
hypoxia was identical in hyperoxic and control animals, implying a normal functioning of EPO-producing cells. The loss of HPV observed in adult rats and caused by perinatal
hyperoxia, comparable to
oxygen therapy in premature infants, might represent a previously unrecognized complication of such a medical intervention capable of aggravating medical conditions such as regional
pneumonias,
atelectases or general anaesthesia in adult life.