Document Detail


High blood levels of nitric oxide in rats subjected to prolonged respiratory arrest and their modulation during adrenocorticotropin-induced resuscitation.
MedLine Citation:
PMID:  9933151     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Anaesthetized rats, endotracheally intubated and mechanically ventilated with room air, were subjected to a 5-min period of asphyxia by turning off the ventilator. The ventilator was then turned back on and, simultaneously, the animals were treated with either the adrenocorticotropin fragment 1-24 [ACTH-(1-24), 160 microg/kg in a volume of 1 ml/kg i.v.] or an equivalent volume of saline. Nitric oxide (NO)-haemoglobin formation was detected ex vivo in arterial blood by electron spin resonance spectrometry; arterial blood pressure, electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for a 60-min observation period, or until prior death. During asphyxia, there was massive formation of NO (red cell concentrations 40-80 microM), associated with a dramatic fall in mean arterial pressure and pulse pressure, marked bradycardia and ECG signs of ischaemic damage, as well as an isoelectric EEG. Treatment with ACTH-(1-24) produced a prompt (within 15 min) and long-lasting drop in NO blood levels, associated with an almost immediate (within 1 min) restoration of cardiovascular function and with a more gradual recovery of EEG, which became normal after 3040 min; all parameters remained stable throughout the 60-min observation period. In saline-treated rats, on the other hand, there was a further increase in NO blood levels, as detected 3 min after treatment, and all died within 5-8 min. Moreover, pretreatment and treatment with S-methylisothiourea sulphate (SMT, 3 mg/kg i.v.), a relatively specific inhibitor of inducible NO synthase, inhibited NO formation, but did not affect the mortality rate (100% within 5-8 min). The present results provide the first evidence that prolonged asphyxia is associated with high blood concentrations of NO, and that the life-saving effect of melanocortin peptides in severe hypoxic conditions is associated with a complete normalization of NO blood levels. However, the lack of SMT protection in this experimental model seems to rule out the possibility that the ACTH-(1-24)-induced resuscitation is due to an effect on NO overproduction.
Authors:
C Bazzani; A Bini; M M Cainazzo; E Meletti; A Tomasi; A Bertolini; S Guarini
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  359     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-06-01     Completed Date:  1999-06-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  53-9     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy. farmacol@unimo.it
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MeSH Terms
Descriptor/Qualifier:
Adrenocorticotropic Hormone / pharmacology*
Animals
Blood Pressure / drug effects,  physiology
Cardiopulmonary Resuscitation
Electrocardiography
Electron Spin Resonance Spectroscopy
Electrooculography
Enzyme Inhibitors / pharmacology
Female
Heart Rate / drug effects,  physiology
Hemoglobins / metabolism
Isothiuronium / analogs & derivatives,  pharmacology
Nitric Oxide / blood*
Nitric Oxide Synthase / antagonists & inhibitors
Nitric Oxide Synthase Type II
Rats
Rats, Wistar
Respiration, Artificial
Respiratory Insufficiency / physiopathology*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Hemoglobins; 10102-43-9/Nitric Oxide; 22584-04-9/Isothiuronium; 2986-19-8/S-methylisothiopseudouronium; 9002-60-2/Adrenocorticotropic Hormone; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat

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