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Long-term effects of prenatal indomethacin administration on the pulmonary circulation in rats
J Herget1, V Hampl, V Povýsilová
1Dept of Physiology, 2nd Medical School, Charles University, Prague, Czech Republic.
Insights
Perinatal pulmonary hypertension, induced by indomethacin in rats, permanently alters pulmonary vasculature mechanics. These changes persist into adulthood, affecting vascular responses to hypoxia.
Area of Science:
- Pulmonary Medicine
- Cardiovascular Physiology
- Developmental Biology
Background:
- Perinatal pulmonary hypertension can impact adult pulmonary vasculature mechanics.
- Previous studies focused on hypoxia-induced pulmonary hypertension.
Purpose of the Study:
- To investigate the long-term effects of non-hypoxic perinatal pulmonary hypertension on rat pulmonary vasculature.
- To determine if indomethacin-induced perinatal pulmonary hypertension causes lasting changes in pulmonary arterial pressure and vascular reactivity.
Main Methods:
- Indomethacin was administered to pregnant rats, inducing pulmonary hypertension in newborns.
- Adult offspring were assessed for pulmonary arterial pressure, vascular remodeling, and pressure/flow relationships in isolated lungs.
- Vascular reactivity to acute hypoxia was evaluated.
Main Results:
- Newborns exhibited increased muscularization of peripheral pulmonary vessels.
- Adult pulmonary arterial pressure was not significantly different between groups.
- Isolated lungs from indomethacin-treated rats showed altered pressure/flow relationships and increased responsiveness to acute hypoxia.
Conclusions:
- Perinatal pulmonary hypertension, even when non-hypoxic, permanently modifies pulmonary vasculature.
- These modifications lead to altered vascular mechanics and reactivity in adulthood, similar to changes observed after perinatal hypoxia.
Abstract:
Mechanical properties of the adult pulmonary vasculature are affected by perinatal experience of hypoxic pulmonary hypertension. In the present study, we followed the long-term effects of perinatal pulmonary hypertension induced by means other than hypoxia in rats. Daily injections 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 pressure (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 exposure to chronic hypoxia or by acute hypoxic challenges was similar in indomethacin-treated and control rats. Normoxic perfusion pressure/flow (P/Q) plots in isolated lungs were less steep in indomethacin-treated than in control rats. Acute hypoxia increased the slope of P/Q plots in indomethacin treated rats but not in controls. The described changes in the pulmonary vasculature induced by indomethacin are similar to those found previously in adult rats born in hypoxia. We conclude that perinatal pulmonary hypertension permanently modifies the pulmonary vasculature.