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
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
Externí odkaz: