Korean J Physiol Pharmacol.
1997 Dec;1(6):673-679.
Role of nitric oxide in ischemia-evoked release of norepinephrine from
rat cortex slices
- Affiliations
-
- 1Department of Pharmacology, Chonbuk National University, Chonju 561-180, South Korea.
- 2Department of Anesthesiology, Chonbuk National University, Chonju 561-180, South Korea.
- 3Institute for Medical Sciences, Chonbuk National University, Chonju 561-180, South Korea.
Abstract
-
It has been generally accepted that glutamate mediates the ischemic
brain damage, excitotoxicity, and induces release of neurotransmitters,
including norepinephrine (NE), in ischemic milieu. In the present
study, the role of nitric oxide (NO) in the ischemia-induced
(3H)norepinephrine((3H)NE) release from cortex slices of the rat was
examined. Ischemia, deprivation of oxygen and glucose from Mg2+/-free
artificial cerebrospinal fluid, induced significant release of (3H)NE
from cortex slices. This ischemia-induced (3H)NE release was
significantly attenuated by glutamatergic neurotransmission modifiers.
NG-nitro-L-arginine methyl ester (L-NAME), NG-monomethyl-L-arginine
(L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors
attenuated the ischemia-evoked (3H)NE release. Hemoglobin, a NO
chelator, and 5, 5-dimethyl-L-pyrroline-N-oxide (DMPO), an electron
spin trap, inhibited (3H)NE release dose-dependently. Ischemia-evoked
(3H)NE release was inhibited by methylene blue, a soluble guanylate
cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable
cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and
S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These
results
suggest that the ischemia-evoked (3H)NE release is mediated by
NMDA receptors, and activation of NO system is involved.