AMINOETHYL-ISOTHIOUREA INHIBITS THE INCREASE IN PLASMA ENDOTHELIN-1 CAUSED BY SEROGROUP A STREPTOCOCCI AND PROLONGS SURVIVAL IN RAT PERITONEAL SEPSIS
| Autor: | G. Lermark, E. A. Hoiby, T. Saetre, Torstein Lyberg, T. Aspelin, Aud Svindland, Egeland T |
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| Rok vydání: | 2001 |
| Předmět: |
Endothelin Receptor Antagonists
Male Time Factors Streptococcus pyogenes medicine.drug_class Nitric Oxide Synthase Type II Blood Pressure Pharmacology Biology Critical Care and Intensive Care Medicine Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Streptococcal Infections Intensive care medicine Animals Enzyme Inhibitors Antihypertensive Agents chemistry.chemical_classification Sulfonamides Reactive oxygen species Endothelin-1 Thiourea Bosentan Receptor Endothelin A Receptor antagonist Shock Septic Endothelin 1 Rats Survival Rate Nitric oxide synthase chemistry Biochemistry Mechanism of action Emergency Medicine biology.protein Nitric Oxide Synthase medicine.symptom medicine.drug |
| Zdroj: | Shock. 15:446-452 |
| ISSN: | 1073-2322 |
| DOI: | 10.1097/00024382-200115060-00006 |
| Popis: | To elucidate the possible roles of nitric oxide (NO), endothelin-1 (ET-1), and reactive oxygen species (ROS) in the pathophysiology of serogroup A streptococcal (GAS) peritoneal sepsis, we investigated the effects of aminoethylisothiourea (AE-ITU), an inducible NO synthase (iNOS) inhibitor, and a ROS scavenger, and the ET-1 receptor antagonist bosentan. In rats, live GAS inocula, 3 x 10(8) and 1 x 10(9) cfu/kg, entailed a 24-h mortality of 10% and 90%, respectively. GAS caused increases in tissue iNOS activity (9 h), in serum nitrite/nitrate (9-24 h), and in intracellular leukocyte ROS levels (3-6 h). These changes were all prevented by the pre-treatment with AE-ITU. A novel finding was that AE-ITU also prevented the GAS-induced marked increase in plasma ET-1 at 6 h. Short-term (7-h) survival was improved by both AE-ITU and by bosentan. The mechanism(s) for the beneficial effects of AE-ITU may possibly be a combined mode of action; iNOS inhibition, ROS scavenging, and inhibition of the increase in plasma ET-1 caused by GAS. |
| Databáze: | OpenAIRE |
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