Persistent pulmonary hypertension (PPH) corresponds to an increase in pulmonary arterial resistance, with in the most severe forms, right heart failure. The persistent pulmonary hypertension of the newborn (PPHN) is estimated at 2/100 births in France. The cardiorespiratory adaptation at birth involves the simultaneous triggering of several phenomena including non completions. Our work aimed to increase knowledge on the regulation of perinatal pulmonary and consider new therapeutic possibilities. Thus, we have demonstrated in vivo pulmonary vasoconstriction in the fetus when maternal passive smoking, by blocking the NO pathway. Similarly, we demonstrated the vasoconstrictor effect of apelin infusion on the pulmonary arteries of fetal sheep. This effect appears dose dependent, inhibited by the action of calcium channel blockers. Instead we have shown a vasodilatory effect of dehydroepiandrosterone (DHEA). This action is mediated by the NO pathway. In parallel, we have shown that polyunsaturated fatty acids ω 3 (AGPIω3) would cause pulmonary vasodilation, extending beyond an hour after stopping the infusion. This effect is mediated by the opening of potassium channels and independent of the NO pathway. Among AGPIω3, we found that eicosapentaenoic acid (EPA) that induces this response without deleterious effect on the systemic circulation or tissue oxygenation. Finally, we established that the antenatal tracheal occlusion (TO), treatment proposed for some malformative pulmonary hypoplasia, does not alter pulmonary blood flow, promoting lung expansion. But in case of prolonged OT, these effects are partly masked by the mechanical effects of intraluminal pressure. And through this work, we have made progress in understanding the adaptation of the pulmonary circulation of the intra to extrauterine life. They also suggest new therapeutic, like supplementation as AGPIω for women expecting a child at risk for PAH, and to consider new possibility of therapeutic research like the way of apelin.
