title: Effects of hypoxia-reoxygenation on microvascular endothelial function in the rat hippocampal slice.
abstract: 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 microm) were measured using image analysis. After preconstriction with prostaglandin F2alpha 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 microM) caused similar dilation before and after hypoxia (mean +/- SEM: 9.6 +/- 0.6% vs. 13.0 +/- 0.9%). Acetylcholine (100 microM) 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.
authors.affiliation: Department of Anesthesiology, The Medical College of Wisconsin, Children's Hospital of Wisconsin, and The Zablocki Veterans Affairs Medical Center, Milwaukee 53226, USA.
authors.forename: M
authors.initials: M
authors.lastname: Stauton
authors.forename: C
authors.initials: C
authors.lastname: Drexler
authors.forename: M G
authors.initials: MG
authors.lastname: Dulitz
authors.forename: D C
authors.initials: DC
authors.lastname: Ekbom
authors.forename: W T
authors.initials: WT
authors.lastname: Schmeling
authors.forename: N E
authors.initials: NE
authors.lastname: Farber
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001784:Blood Gas Analysis; D004730:Endothelium, Vascular / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008833:Microcirculation; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine