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 [mu]m) were measured using image analysis. After preconstriction with prostaglandin F2[alpha] and controlled p H 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 [mu]M) caused similar dilation before and after hypoxia (mean +/- SEM: 9.6 +/- 0.6%vs. 13.0 +/- 0.9%). Acetylcholine (100 [mu]M) 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%).