Inhibitory effects of diclofenac on the endotoxin shock response in relation to endothelin turnover in the pig
| Autor: | Jan M. Lundberg, Eddie Weitzberg, Anders Rudehill |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Diclofenac Swine Hypertension Pulmonary Blood Pressure Arachidonic Acids Sepsis Norepinephrine chemistry.chemical_compound Heart Rate Internal medicine Escherichia coli medicine Animals Cyclooxygenase Inhibitors Neuropeptide Y Cardiac Output Lung biology business.industry Endothelins General Medicine medicine.disease Shock Septic Pulmonary hypertension Endotoxins Anesthesiology and Pain Medicine medicine.anatomical_structure Endocrinology chemistry Enzyme inhibitor Shock (circulatory) Vascular resistance biology.protein Vascular Resistance Arachidonic acid medicine.symptom Endothelin receptor business medicine.drug |
| Zdroj: | Acta Anaesthesiologica Scandinavica. 39:50-59 |
| ISSN: | 0001-5172 |
| DOI: | 10.1111/j.1399-6576.1995.tb05592.x |
| Popis: | During sepsis vasoactive arachidonic acid metabolites of the cyclo-oxygenase pathway and the endothelium-derived vasoconstrictor endothelin-1 (ET-1) are released. The effects of cyclo-oxygenase pathway inhibition by diclofenac on the endotoxin shock response and ET-1 turnover, were investigated in five groups of pigs. In the first group (n = 7; controls) endotoxin (15μg·kg−1·h−1 i.v.) was infused for two hours. In a second endotoxin group (n = 7), the animals were pretreated with diclofenac (3 mg·kg−1 i.v.). In a third group (n = 7), high-dose ET-1 was infused (20 pmol·kg−1·min−1 i.v.) and in a fourth group (n = 7), the ET-1 infusion was preceded by diclofenac. In a fifth group (n = 4), a low and intermediate dose of ET-1 (0.2 and 4 pmol· kg−1·min−1) was infused. A significant increase in ET-1-like immunoreactivity (LI) plasma levels was observed in both endotoxin groups, but in the diclofenac group the increase was comparatively delayed. Furthermore, this group showed a more stable haemodynamic course and in the biphasic increase of pulmonary vascular resistance seen in endotoxin controls, the initial peak was abolished by diclofenac. Exogenous ET-1 infusion indicated that not only locally released but possibly also circulating ET-1 could be a mediator of vascular responses to endotoxin. Indications of release from the lungs were seen during endotoxin infusion. Diclofenac had no effect on basal ET-1-LI plasma levels or on the disappearance rate from plasma of ET-1-LI and the haemodynamic changes seen on ET-1 infusion. The inhibition of cyclo-oxygenase pathway by diclofenac resulted in prevention of the initial pulmonary hypertension and a delayed increase in plasma ET-1-LI levels in porcine endotoxin shock and this latter effect is not due to an increased rate of disappearance from plasma but rather to a decreased release of ET-1. |
| Databáze: | OpenAIRE |
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