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 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.
Stauton
M
M
Department of Anesthesiology, The Medical College of Wisconsin, Children's Hospital of Wisconsin, and The Zablocki Veterans Affairs Medical Center, Milwaukee 53226, USA.
Drexler
C
C
Dulitz
M G
MG
Ekbom
D C
DC
Schmeling
W T
WT
Farber
N E
NE
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
D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine