Actions of S-nitrosocysteine in the nucleus tractus solitarii are unrelated to release of nitric oxide.
Cardiovascular effects elicited by microinjection of L-S-nitrosocysteine in the nucleus tractus solitarii (NTS) were compared and contrasted with those produced by the dextroisomer, other nitric oxide donors and nitric oxide itself. L-S-nitrosocysteine produced dose-related decreases of arterial pressure and heart rate. In contrast, D-S-nitrosocysteine, S-nitrosoglutathione, glyceryl trinitrate, and sodium nitroprusside produced minimal responses that were not dose-related. Likewise, injection of cystine and nitric oxide, two products of S-nitrosocysteine breakdown, produced no significant response. Headspace analysis using chemiluminescence revealed that L- and D-S-nitrosocysteine released identical amounts of nitric oxide when exposed to homogenates of whole rat brain. Responses to L-S-nitrosocysteine were not affected by local injection of oxyhemoglobin or the nitric oxide synthase inhibitor L-nitroarginine methylester. Although injection of L-cysteine into the NTS produced responses similar to those seen with injection of L-S-nitrosocysteine, blockade of excitatory amino acid receptors with kynurenic acid inhibited responses to cysteine but not those to the nitrosothiol. The study demonstrates that S-nitrosocysteine is biologically active in the NTS. Its action is independent of release of nitric oxide from the nitrosothiol but may be mediated through stereoselective sites on target neurons.
Ohta
H
H
Department of Neurology, University of Iowa, Iowa City 52242, USA.
Bates
J N
JN
Lewis
S J
SJ
Talman
W T
WT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007736:Kynurenic Acid / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D015398:Signal Transduction / Q000187:drug effects; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010108:Oxyhemoglobins; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D007736:Kynurenic Acid; D003545:Cysteine; D019331:NG-Nitroarginine Methyl Ester