Perinatal history of hypoxia leads to lower vascular pressures and hyporeactivity to angiotensin II in isolated lungs of adult rats

The most dramatic changes in pulmonary circulation occur at the time of bir th. We hypothesized that some of the effects of perinatal hypoxia on pulmon ary vessels are permanent. We studied the consequences of perinatal exposur e to hypoxia (12% O-2 one week before and one week after birth) in isolated lungs of adult male rats (similar to 12 weeks old) perfused with homologou s blood. Perfusion pressure-flow relationship was tilted towards lower pres sures in the perinatally hypoxic as compared to the control, perinatally no rmoxic rats. A non-linear, distensible vessel model analysis revealed that this was due to increased vascular distensibility in perinatally hypoxic ra ts (4.1+/-0.6 %/mm Hg vs. 2.3+/-0.4 %/mm Hg in controls, P = 0.03). Vascula r occlusion techniques showed that lungs of the perinatally hypoxic rats ha d lower pressures at both the pre-capillary and post-capillary level. To as sess its role, basal vascular tone was eliminated by a high dose of sodium nitroprusside (20 muM) This reduced perfusion pressures only in the lungs o f rats born in hypoxia, indicating that perinatal hypoxia leads to a perman ent increase in the basal tone of the pulmonary vessels. Pulmonary vasocons trictor reactivity to angiotensin II (0.1-0.5 mug) was reduced in rats with the history of perinatal hypoxia. These data show that perinatal hypoxia h as permanent effects on the pulmonary circulation that may be beneficial an d perhaps serve to offset the previously described adverse consequences.