Neonatal hypoxia protects against hypoxic adaptation pulmonary vasculature in adults

Abstract

We investigated whether neonatal hypoxia altered the subsequent adaptation to hypoxia in adults. 3 groups of neonatal rats were used: NNH rats were normoxic for 6 weeks then hypoxic for 4 weeks; HNH rats were hypoxic for 2 weeks, normoxic for 4 weeks, then hypoxic for 4 weeks; NNN rats were normoxic for 10 weeks. The pulmonary circulation was perfused in-situ: perfusion pressure was 17.6 ± 3.4, 40.9 ± 6.0 and 31.5 ± 2.7 mmHg in NNN, NNH and HNH rats, respectively. Endothelin (10μM) increased perfusion pressure to 21.5 ± 2.7, 52.9 ± 6.4 and 40.9 ± 3.1 mmHg in NNN, NNH and HNH rats. Endothelin dose-response curves of isolated pulmonary arterial rings were similar in all groups at 6 weeks (prior to the second hypoxic exposure); rings from NNH rats showed depressed ETA-mediated constriction at 10 weeks (after the hypoxic exposure), whereas those from HNH rats were similar to NNN. Rats were returned to normoxia for a further 4 weeks: endothelin (500μM) increased vascular contraction by 123 ± 7, 188 ± 6 or 83 ± 11 % in NNN, NNH or HNH. These data suggest that brief exposure to hypoxia in the neonatal period confers protection against pulmonary vascular hypertrophy and altered vascular reactivity upon exposure to hypoxia as an adult. Funded by The Institute of Cardiovascular Science & Medicine, Hong Kong.