Nitric oxide contributes to dilatation of cerebral arterioles during seizures.
Endogenous release of excitatory amino acids during seizures produces marked increases in neuronal activity and guanosine 3',5'-cyclic monophosphate levels in brain tissue, which are mediated by nitric oxide (NO). We tested the hypothesis that dilatation of the cerebral microcirculation during seizures is mediated by NO. Diameters of cerebral arterioles were measured using a closed cranial window in anesthetized rabbits. Three, five, nine, and eleven minutes after the onset of pentylenetetrazole-induced seizure (which releases endogenous excitatory amino acids), arteriolar diameter increased by 42 +/- 6, 30 +/- 3, 20 +/- 2, and 16 +/- 2% (means +/- SE), respectively, from a control diameter of 86 +/- 6 microns. Arterial pressure was maintained at control levels during seizures. In the presence of NG-nitro-L-arginine (L-NNA, 300 microM), an inhibitor of NO synthase, vasodilatation during seizures was not affected at 3 min (40 +/- 8%) but was significantly reduced at 5, 9, and 11 min (17 +/- 5, 6 +/- 3, and 1 +/- 3%, respectively, P < 0.05 vs. control). Vasodilatation in response to topical application of acetylcholine (1 microM) was also inhibited by L-NNA (33 +/- 5 vs. 3 +/- 2%, P < 0.05). Dilatation of cerebral arterioles in response to nitroprusside (1 and 10 microM) was not inhibited by L-NNA. Thus sustained, but not initial, dilatation of cerebral arterioles during seizures appears to be mediated in part by NO.
Faraci
F M
FM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Breese
K R
KR
Heistad
D D
DD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011817:Rabbits; D012640:Seizures / Q000503:physiopathology*; D014664:Vasodilation / Q000502:physiology*
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D010433:Pentylenetetrazole