Hypoxia-induced brain angiogenesis in the adult rat.

1. Prolonged hypoxia increases the brain vascularity. Here we studied the protein and deoxyribonucleic acid (DNA) content of isolated cerebral microvessels in hypoxic and control rats. 2. Adult male Wistar rats that were subjected to hypobaric hypoxia at 50.5 kPa (0.5 atm) for periods of 1, 2, or 3 weeks and normoxic littermate controls were used. Cerebral microvessels were harvested by bulk isolation from the pooled cortical mantles of three to six rats in each group. The isolated microvessels were assayed for their protein and DNA content. 3. Microvessel protein yield increased from 0.31 to 0.45 mg of microvessel protein (g wet wt)-1 of cerebral cortex after 1 week of hypoxia, but did not increase further during up to 3 weeks of hypoxia. In contrast, microvessel DNA yield did not increase during the first week of hypoxia, but increased significantly after 2 weeks of hypoxia and continued to increase up to 56 micrograms of microvessel DNA (g cerebral cortex)-1 at 3 weeks of hypoxia (normoxic mean was 32 micrograms DNA g-1). 4. The cell size index (mg protein:mg DNA) of isolated cerebral microvessels increased after 1 week of hypoxia, suggesting microvascular hypertrophy, but returned to control by the second week of hypoxia and decreased to below control levels by the third week of hypoxia, suggesting microvascular hyperplasia. These results indicate that the increased vascularity of the brain in hypobaric hypoxia progresses from an early phase of microvascular hypertrophy to later microvascular hyperplasia.