Effects of the nitric oxide donor, DEA/NO on cortical spreading depression

Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) delayed mar...

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Veröffentlicht in:Neuropharmacology 2003-06, Vol.44 (7), p.949-957
Hauptverfasser: Wang, M., Obrenovitch, T.P., Urenjak, J.
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creator Wang, M.
Obrenovitch, T.P.
Urenjak, J.
description Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid-base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 μM) had little effect on CSD by itself, but it reversed in a concentration-dependent manner the effects of NOS inhibition by 1 mM L-NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. In this case, the molecular targets for NO may be located either on brain cells to suppress mechanisms directly involved in CSD genesis, or on local blood vessels to couple flow to the increased energy demand associated with CSD.
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These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. 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We reported previously that the local inhibition of nitric oxide (NO) synthesis with Nω-nitro-L-arginine methyl ester (L-NAME) delayed markedly the initiation of the recovery of ionic homeostasis from CSD. Here we describe a novel method for selective, controlled generation of exogenous NO in a functioning brain region. It is based on microdialysis perfusion of the NO donor, 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA/NO). As DEA/NO does not generate NO at alkaline pH, and as the brain has a strong acid-base buffering capacity, DEA/NO was perfused in a medium adjusted at alkaline (but unbuffered) pH. Without DEA/NO, such a microdialysis perfusion medium did not alter CSD. DEA/NO (1, 10 and 100 μM) had little effect on CSD by itself, but it reversed in a concentration-dependent manner the effects of NOS inhibition by 1 mM L-NAME. These data demonstrate that increased formation of endogenous NO associated with CSD is critical for subsequent, rapid recovery of cellular ionic homeostasis. 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inhibitors</topic><topic>Nitric Oxide Synthase Type I</topic><topic>Nitrogen Oxides</topic><topic>NO donor</topic><topic>Nω-nitro-L-arginine methyl ester (L-NAME)</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, M.</creatorcontrib><creatorcontrib>Obrenovitch, T.P.</creatorcontrib><creatorcontrib>Urenjak, J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, M.</au><au>Obrenovitch, T.P.</au><au>Urenjak, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the nitric oxide donor, DEA/NO on cortical spreading depression</atitle><jtitle>Neuropharmacology</jtitle><addtitle>Neuropharmacology</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>44</volume><issue>7</issue><spage>949</spage><epage>957</epage><pages>949-957</pages><issn>0028-3908</issn><eissn>1873-7064</eissn><coden>NEPHBW</coden><abstract>Cortical spreading depression (CSD) is a transient disruption of local ionic homeostasis that may promote migraine attacks and the progression of stroke lesions. 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subjects Animals
Biological and medical sciences
Cortical spreading depression
Cortical Spreading Depression - drug effects
Diethylamines - pharmacology
Electroencephalography - drug effects
Enzyme Inhibitors - pharmacology
Extracellular Space - drug effects
Extracellular Space - physiology
High extracellular potassium
Ionic homeostasis
Male
Medical sciences
Microdialysis
NG-Nitroarginine Methyl Ester - pharmacology
Nitric oxide
Nitric Oxide Donors - pharmacology
Nitric oxide synthase
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase Type I
Nitrogen Oxides
NO donor
Nω-nitro-L-arginine methyl ester (L-NAME)
Rats
Rats, Sprague-Dawley
title Effects of the nitric oxide donor, DEA/NO on cortical spreading depression
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