Endothelial and subintimal changes in rat hilar pulmonary artery during recovery from hypoxia. A quantitative ultrastructural study

Abstract

Whereas hypoxia is known to cause an increase in thickness of both the medial and adventitial layers of the muscular pulmonary arteries, little is known of its effect on the endothelial cell and rest of the intima. The present study describes the ultrastructural changes in the intima of the hilar intrapulmonary muscular artery of the rat after exposure to hypobaric hypoxia of 380 torr for 10 days and their resolution during recovery periods of between 3 and 70 days in room air. After 10 days of hypoxia, the intima is 3 times thicker than the controls (control = 1.81 micrometers. +/- 0.13 standard error (S.E.); hypoxia = 5.59 micrometers. +/- 1.14 S.E.; p less than 0.05). The thickness of the endothelial cell layer doubles (control = 1.57 +/- 0.12 S.E.; hypoxia = 3.29 micrometer. +/- 0.23 S.E.; p less than 0.001) and point-counting the cytoplasm of these cells reveal significant relative increase in areal proportions, and hence most marked hypertrophy, of ribosomes, rough endoplasmic reticulum, and Golgi apparatus. An increase in number of endothelial cells is also apparent. The increase in thickness of the subendothelial layer is due to appearance of edema. In addition, microfibrillar basement membrane-like material is found focally within the subendothelial layer. In some sections, approximately 50 per cent of the endothelial associated basement membrane is absent. During recovery periods, there is regression of all the hypoxia-induced changes, save that the amount of subendothelial elastin increases to day 28 recovery, thereby altering the structure of the wall. The presence of elastin, collagen fibers, and microfibrils on the luminal side of the endothelial basement membrane, in control and experimental animals, points to their synthesis by the endothelial cell.