Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation
Autor: | Zhao-Qin Cheng, Hans Jacobs, Luis E. Santos Martinez, Steven N. Mink, Krika Kasian, Ratna Bose, R. Bruce Light |
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Rok vydání: | 2008 |
Předmět: |
Time Factors
Physiology Indomethacin Receptors Cytoplasmic and Nuclear Vasodilation Pharmacology Phenylephrine chemistry.chemical_compound Soluble Guanylyl Cyclase Vasoconstrictor Agents Mannitol Enzyme Inhibitors Cyclic GMP Oxadiazoles biology Chemistry Free Radical Scavengers Catalase Nitric oxide synthase medicine.anatomical_structure Biochemistry Shock (circulatory) Aminoquinolines Omega-N-Methylarginine medicine.symptom Cardiology and Cardiovascular Medicine Carotid Artery Internal Signal Transduction Endothelium In Vitro Techniques Nitric Oxide Nitric oxide Dogs Mesenteric Artery Superior Quinoxalines Sepsis Physiology (medical) Cyclic GMP-Dependent Protein Kinases medicine Animals Humans Cyclooxygenase Inhibitors Protein Kinase Inhibitors omega-N-Methylarginine Dose-Response Relationship Drug Ethanol Septic shock Hydrogen Peroxide Thionucleotides medicine.disease Hydroquinones Methylene Blue Guanylate Cyclase Prostaglandins biology.protein Muramidase Nitric Oxide Synthase Soluble guanylyl cyclase |
Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 294:H1724-H1735 |
ISSN: | 1522-1539 0363-6135 |
Popis: | In septic shock, systemic vasodilation and myocardial depression contribute to the systemic hypotension observed. Both components can be attributed to the effects of mediators that are released as part of the inflammatory response. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression that develops in a canine model of septic shock. Lzm-S binds to the endocardial endothelium, resulting in the production of nitric oxide (NO), which, in turn, activates the myocardial soluble guanylate cyclase (sGC) pathway. In the present study, we determined whether Lzm-S might also play a role in the systemic vasodilation that occurs in septic shock. In a phenylephrine-contracted canine carotid artery ring preparation, we found that both canine and human Lzm-S, at concentrations similar to those found in sepsis, produced vasorelaxation. This decrease in force could not be prevented by inhibitors of NO synthase, prostaglandin synthesis, or potassium channel inhibitors and was not dependent on the presence of the vascular endothelium. However, inhibitors of the sGC pathway prevented the vasodilatory activity of Lzm-S. In addition, Aspergillus niger catalase, which breaks down H2O2, as well as hydroxyl radical scavengers, which included hydroquinone and mannitol, prevented the effect of Lzm-S. Electrochemical sensors corroborated that Lzm-S caused H2O2 release from the carotid artery preparation. In conclusion, these results support the notion that when Lzm-S interacts with the arterial vasculature, this interaction results in the formation of H2O2, which, in turn, activates the sGC pathway to cause relaxation. Lzm-S may contribute to the vasodilation that occurs in septic shock. |
Databáze: | OpenAIRE |
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