Changes of fibronectin in the right and left ventricles of rats exposed to chronic normobaric hypoxia.

Abstract

Changes of fibronectin (FN) in the right and left ventricles of adult rats exposed to chronic normobaric hypoxia were observed by a peroxidase immunohistochemical stain technique and analyzed quantitatively by a point counting method. Fifty-six rats were randomly divided into control groups of day 0 (immediately prior to the experiment), day 5, day 15, and day 30 and hypoxia groups of day 5, day 15, and day 30. Rats of the hypoxia groups were put into a normobaric hypoxia chamber with oxygen concentration adjusted to 10 percent. The rats of the control groups breathed room air. From day 5 on, the ratio of the weight of the right ventricle (RV) to that of the left ventricle (LV) plus interventricular septum (SP), RV/(LV+SP), and the ratio of the weight of the right ventricle (RV) to the body weight (BW), RV/BW, in the hypoxia groups increased significantly as compared with those of the control groups. The amount of immunoreactive FN in the right ventricle increased significantly in the hypoxia groups after exposure to hypoxia environment for 15 days (10.31% +/- 2.15%, mean +/- S.D.) and for 30 days (9.55% +/- 1.65%) as compared with those in the day 0 control group (3.05% +/- 1.15%, p < 0.01), the day 15 control group (3.26% +/- 0.83%, p < 0.01), and the day 30 control group (3.19% +/- 0.51%, p < 0.01). However, there were no significant changes in the amount of immunoreactive FN in the left ventricle of the hypoxia groups as compared with the control groups. These results suggest that chronic hypoxia may lead to an increase of FN in the hypertrophied right ventricle but not in the left ventricle, which indicates that pulmonary hypertension induced by chronic hypoxia rather than chronic hypoxia itself is a major cause for the increase of FN in the myocardium. The increased FN in the right ventricle may accelerate the accumulation of collagen and, in turn, contribute to the increase of the myocardial stiffness and eventually to the diastolic dysfunction of the hypertrophied right ventricle induced by chronic hypoxia.