Phospholipase A2-induced pulmonary and hemodynamic responses in the guinea pig. Effects of enzyme inhibitors and mediators antagonists
| Autor: | Stephen K. Durham, Joel E. Tocker, W. M. Selig, Ann F. Welton |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Pulmonary and Respiratory Medicine
Male Indazoles Guinea Pigs Indomethacin Hemodynamics Blood Pressure Bronchi Pharmacology Dexamethasone Phospholipases A Guinea pig Phospholipase A2 Pressure Medicine Animals Humans Platelet Enzyme Inhibitors Platelet Activating Factor Lung Pyrilamine biology business.industry Antagonist Azepines Triazoles Propranolol Trachea Phospholipases A2 Blood pressure Anesthesia biology.protein lipids (amino acids peptides and proteins) SRS-A Cyclooxygenase business Bronchoalveolar Lavage Fluid medicine.drug |
| Zdroj: | The American review of respiratory disease. 142(5) |
| ISSN: | 0003-0805 |
| Popis: | The effect of phospholipase A2 (Naja naja) PLA2) on mean arterial blood pressure and intratracheal pressure was examined in anesthetized guinea pigs. Intracheally administered PLA2 (1 to 10 U) produced acute, dose-dependent increases in mean arterial blood pressure and intracheal pressure. However, Intravenously administered PLA2 (doses as large as 1,000 U) did not alter monitored variables. Acute PLA2-induced morphologic alterations were characterized by airway constriction, airway/alveolar cell damage, and pulmonary sequestration of both leukocytes and platelets. PLA2-induced increases in both mean arterial blood pressure and intratracheal pressure were attenuated to varying degrees by pretreating intravenously with indomethacin (10 mg/kg), a cyclooxygenase inhibitor, and WEB 2086 (0.1 mg/kg), a platelet-activating factor antagonist. Both ICI 198,615 (1 mg/kg), a leukotriene D4, receptor antagonist given intravenously, and dexamethasone (50 mg/kg), a steroidal anti-inflammatory agent given intraperitoneally as a 2-day pretreatment, reduced PLA2-induced increases in intratracheal pressure. Pyrilamine (2 mg/kg), a histamine1-receptor antagonist given intravenously, did not modify PLA2-induced pathophysiologic responses. Guinea pigs exposed to aerosolized PLA2 (100 U/ml) exhibited evidence of increased bronchoalveolar lavage macrophage, leukocyte, and lymphocyte accumulation at 24 h post-PLA2. These studies suggest that in vivo PLA2-induced pathophysiologic changes in the guinea pig involve alterations in resident airway cell populations as well as sequestration and infiltration of inflammatory cells. Both eicosanoids and platelet-activating factor appear to contribute to these PLA2-induced pathophysiologic effects. |
| Databáze: | OpenAIRE |
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