ULTRASTRUCTURE OF RAT PULMONARY ARTERIOLES AFTER NEONATAL EXPOSURE TO HYPOXIA AND SUBSEQUENT RELIEF AND TREATMENT WITH MONOCROTALINE

A group of rats was born in and spent the first 4 weeks of life at a simulated altitude of 3550 m. Two animals were killed immediately afterwards and the remaining 16 were allowed to recover for various times up to a maximum of 12 weeks at sea-level atmospheric pressure. On ultrastructural examination, the pulmonary arterioles of hypoxic rats showed muscularization, the new layer of mature smooth muscle cells containing abundant organelles and myofilaments. These cells were bounded by prominent elastic laminae. During the recovery period, the medial layer became progressively thinned, but the cells still retained some characteristics of smooth muscle by 12 weeks' recovery. When a similar group of ten hypoxic rats was allowed to recover for 12 weeks before being given monocrotaline, there was early enlargement of the residual smooth muscle cells in the media of pulmonary arterioles and within 5 weeks there was again a thick layer of medial smooth muscle. This was in contrast to the sparse, weakly muscularized arterioles seen in eight similarly treated rats born under normoxic conditions. The relevance is discussed of these findings to the rare occurrence of primary pulmonary hypertension in people who were born at high altitude but returned to sea-level during childhood.