Dilatation of cerebral arterioles in response to lipopolysaccharide in vivo.
OBJECTIVE
Bacterial lipopolysaccharide can increase nitric oxide (NO) production by expression of an inducible form of NO synthase. Bacterial infections of the central nervous system dilate cerebral vessels and increase blood flow. We hypothesized that topical application of bacterial lipopolysaccharide would increase production of NO, causing dilatation of cerebral arterioles.


METHODS
Cranial windows were implanted in anesthetized rabbits. Windows were flushed with artificial cerebrospinal fluid, artificial cerebrospinal fluid with lipopolysaccharide, or artificial cerebrospinal fluid with lipopolysaccharide and NG-monomethyl-L- arginine (an inhibitor of NO synthase) for 4 hours. Other rabbits received either dexamethasone or indomethacin intravenously 1 hour before lipopolysaccharide treatment of cranial windows.


RESULTS
Application of lipopolysaccharide in cranial windows produced marked, progressive vasodilation, with diameter increased by 58 +/- 7% (mean +/- SEM) after 4 hours. The cerebral vasodilator response was inhibited by NG-monomethyl-L-arginine, dexamethasone, or indomethacin. Excess L-arginine reversed the inhibitory effect of NG-monomethyl-L-arginine.


CONCLUSIONS
Inhibition of lipopolysaccharide-induced dilatation of cerebral arterioles by NG-monomethyl-L-arginine and dexamethasone suggests that a portion of the vasodilation was mediated by inducible NO synthase. Indomethacin also inhibited lipopolysaccharide-induced vasodilatation. These findings suggest an important role for both nitric oxide and cyclooxygenase products in lipopolysaccharide-induced cerebral arteriolar dilatation in vivo.
Brian
J E
JE
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242.
Heistad
D D
DD
Faraci
F M
FM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
D008070:Lipopolysaccharides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007213:Indomethacin