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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1724    most recent 01072.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mink, S. N. Articles by Light, R. B. Search for Related Content PubMed PubMed Citation Articles by Mink, S. N. Articles by Light, R. B.

Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation

Departments of ¹Medicine, ²Pharmacology and Therapeutics, and ³Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada; and ⁴Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico

Submitted 15 September 2007 ; accepted in final form 6 February 2008

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.

reactive oxygen species; catalase; compound I; hydroxyl radical; septic shock; hypotension

This article has been cited by other articles:

				S. N Mink, H. Jacobs, Z.-Q. Cheng, K. Kasian, L. E Santos-Martinez, and R. B. Light Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H930 - H948. [Abstract] [Full Text] [PDF]