LONG-TERM EFFECTS OF PRENATAL INDOMETHACIN ADMINISTRATION ON THE PULMONARY CIRCULATION IN RATS

Mechanical properties of the adult pulmonary vasculature are affected by perinatal experience of hypoxic pulmonary hypertension. In the pres ent study, we followed the long-term effects of perinatal pulmonary hy pertension induced by means other than hypoxia in rats. Daily injectio ns of indomethacin (1 mg . kg(-1) body weight (BW)) were given to the parturient rats. Their newborn pups had significantly increased number of muscularized peripheral pulmonary vessels. Pulmonary hypertension, however, did not persist to adulthood (mean pulmonary arterial pressu re (Ppa) was 17.2+/-1.3 torr in the experimental group and 16.4+/-0.8 torr in controls). Pulmonary hypertension induced in adult rats by exp osure to chronic hypoxia or by acute hypoxic challenges was similar in indomethacin-treated and control rats. Normoxic perfusion pressure/fl ow (P/Q) plots in isolated lungs were less steep in indomethacin-treat ed than in control rats. Acute hypoxia increased the slope of P/Q plot s in indomethacin treated rats but not in controls. The described chan ges in the pulmonary vasculature induced by indomethacin are similar t o those found previously in adult rats born in hypoxia. We conclude th at perinatal pulmonary hypertension permanently modifies the pulmonary vasculature.