Carotid body (CB) chemoreceptor cells from adult rats that in the perinatal life have been exposed to 55% O₂ have a diminished capacity to respond to hypoxia (Prieto-Lloret et al., J Physiol. 554:126-44, 2004). We have tested the hypothesis that hyperoxia alters the ability of pulmonary artery smooth muscle cells to respond to hypoxia, and thereby to hypoxic pulmonary vasoconstriction (HPV).

Pregnant rats were exposed to an atmosphere of 55% O₂ one week prior to delivery. Litters were reared in the same atmosphere for up to 30 days. Thereafter the animals were transferred to the vivarium and maintained until adulthood (90-100 days). Additional mothers and litters, fed an antioxidant diet (vit E, 400 mg/Kg pellet and lipoic acid 1g/kg pellet), were similarly exposed to hyperoxia. We studied responses of the arterial pulmonary bed in an in situ isolated lung preparation and by transcardiac canulation of the pulmonary artery.

Findings: 1) We confirmed the altered CB functioning in hyperoxic rats. 2) HPV was drastically blunted (by 80%) in hyperoxic rats. 3) NOS inhibition potentiated HPV in controls and had no effect on hyperoxic rats. 4) 4-aminopyridine caused and identical pressor response in control and hyperoxic rats. 5) Thickness of muscular layer was identical in microvessels of control and hyperoxic rats. 6) Antioxidant supplementation restored HPV. Redox status in adulthood was not different in control and hyperoxic animals. Currently we are searching for redox alterations in the first month of life of hyperoxic animals.

Grants: BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (FISS-ICiii) and JCyL-GR242.