Arteriolar remodeling in skeletal muscle of rats exposed to chronic hypoxia.

ABSTRACT

The topological structure of the arteriolar network is an important determinant of microvascular resistance. In several normal and pathological conditions, this network topology is remodeled such that adequate tissue perfusion and oxygenation are maintained. The objective of this study was to quantify the extent of arteriolar remodeling in skeletal muscle of rats chronically exposed to 10% oxygen for 18 +/- 3.6 days. Arcade arteriolar (AA) and transverse arteriolar networks that had been immunofluorescently labeled for smooth muscle alpha-actin and smooth muscle myosin heavy chain were observed in whole-mount gracilis muscles from hypoxic and weight-matched control rats. Eight muscles from 4 animals were used for analysis in each group. The percentage (+/- SD) of terminal arteriolar endings that were positive for smooth muscle alpha-actin, but negative for smooth muscle myosin heavy chain increased significantly (p < 0.05) from 29.2 +/- 8.0 in controls to 70.7 +/- 9.0 in hypoxia, indicating that the rate of terminal arteriolar development was elevated in the hypoxic animals. The number of AA loops/muscle (+/- SD) increased significantly from 9.6 +/- 2.3 in controls to 14.4 +/- 4.6 in hypoxia. This increase in AA loops/muscle was due primarily to a large increase in the number of small-diameter (<15 microm) AA segments/muscle, suggesting that new AA loops were formed via the recent anastomosing of developing small-diameter terminal arterioles. The results demonstrate that exposure to chronic hypoxia stimulates significant remodeling of both the arcade and transverse arteriolar networks in skeletal muscle.