Effects of hypoxia-reoxygenation on microvascular endothelial function in the rat hippocampal slice.

Background: Cerebral ischemia and hypoxia may cause injury to both neuronal and vascular tissue. The direct effects of hypoxia on endothelial function in intraparenchymal cerebral arterioles are unknown. Using a modification of the rat brain slice preparation, allowing continuous imaging of these previously inaccessible vessels, microvessel dilation was evaluated before and after a brief hypoxic episode. Methods: Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arterioles were visualized using computerized videomicroscopy, and their diameters (range, 12-27 μm) were measured using image analysis. After preconstriction with prostaglandin F 2α and controlled pH and carbon dioxide tension, graded concentrations of either acetylcholine (endothelium-dependent vasodilation) or sodium nitroprusside (endothelium-independent vasodilation) were given before and after a 10-min period of hypoxia. Results: Sodium nitroprusside (100 μM) caused similar dilation before and after hypoxia (mean ± SEM: 9.6 ± 0.6% vs. 13.0 ± 0.9%). Acetylcholine (100 μM) caused significantly less dilation (P < 0.05) after hypoxia (mean ± SEM: 9.3 ± 1.8% vs. 3.6 ± 1.2%). The decreased acetylcholine-induced dilation after hypoxia was not reversed by pretreatment with L-arginine (1 mM), the precursor of nitric oxide (mean ± SEM: 8.8 ± 1.3% vs. 4.4 ± 0.7%). Conclusions: Even brief periods of hypoxia may cause endothelial dysfunction in intraparenchymal cerebral arterioles. This does not seem to be related to a deficiency of the nitric oxide substrate, L-arginine. Endothelial dysfunction and impaired endothelium-dependent dilation of microvessels may decrease oxygen delivery and increase neuronal injury during cerebral hypoxia-reoxygenation.