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Am J Physiol Heart Circ Physiol 279: H1571-H1578, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 4, H1571-H1578, October 2000

Three-week neonatal hypoxia reduces blood CGRP and causes persistent pulmonary hypertension in rats

I. M. Keith1, S. Tjen-A-Looi1, H. Kraiczi2, and R. Ekman2

1 Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706; and 2 Section of Experimental Neuroscience, Institute of Clinical Neuroscience, University of Göteborg, Mölndal's Hospital, S-43180 Mölndal, Sweden

To increase understanding of persistent pulmonary hypertension, we examined chronic pulmonary effects of hypoxia at birth and their relationships with immunoreactive levels of the potent vasodilator, calcitonin gene-related peptide (CGRP). Rats were born in 10% hypobaric hypoxia, where they remained for 1-2 days, or in 15% hypoxia, where they remained for 21 days. All were then reared in normoxia for 3 mo followed by reexposure to 10% hypoxia for 7 days (Hright-arrowH) or continued normoxia (Hright-arrowN); age-matched normoxic rats were hypoxic for the last 7 days (Nright-arrowH) or normoxic throughout (Nright-arrowN). Results are as follows. Pulmonary arterial pressure (PPA) in 10% Hright-arrowN rats was normal at the end of the experiment (13 wk), but in rats reexposed to hypoxia (Hright-arrowH), pressure rose to 19% above Nright-arrowH controls. In 15% Hright-arrowN rats, PPA remained high, similar to that of Nright-arrowH rats, and increased further by 40% on reexposure (Hright-arrowH). Medial thickness of small pulmonary arteries in 10% Hright-arrowH rats also increased by 40% over Nright-arrowH controls and was equally high in 15% Hright-arrowN and Hright-arrowH rats. In Nright-arrowH rats from both experiments, right ventricular hypertrophy index (RVH) was increased after hypoxia at 15-16 wk. Also, in the 15% study, RVH remained elevated in Hright-arrowN rats and increased in Hright-arrowH rats by 19% above Nright-arrowH controls. Blood CGRP was reduced by neonate and adult hypoxia, and hypoxic reexposure (Hright-arrowH) further lowered blood CGRP in the 15% but not 10% study. Declining left ventricular blood CGRP correlated highly with logarithmically increasing PPA in the 15% study (r = -0.81, P = 0.000). In conclusion, 1) short perinatal exposure to 10% O2 exacerbated pulmonary hypertension with hypoxia later in life, 2) 15% O2 at birth and for 21 days caused persistent pulmonary hypertension and exacerbation with reexposure, and 3) PPA correlated highly with declining blood CGRP levels in the 15% study.

hypoxic sensitization; persistent hyperventilation; right ventricular hypertrophy; calcitonin gene-related peptide


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