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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/H3140    most recent 00502.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles 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, impairs the cardiac neural adrenergic response by nonendothelial release of NO and inhibitory G protein signaling

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 26 April 2007 ; accepted in final form 29 August 2007

We previously showed that lysozyme (Lzm-S), derived from leukocytes, caused myocardial depression in canine sepsis by binding to the endocardial endothelium to release nitric oxide (NO). NO then diffuses to adjacent myocytes to activate the cGMP pathway. In a canine right ventricular trabecular (RVT) preparation, Lzm-S also decreased the inotropic response to field stimulation (FSR) during which the sympathetic and parasympathetic nerves were simulated to measure the adrenergic response. In the present study, we determined whether the pathway by which Lzm-S decreased FSR was different from the pathway by which Lzm-S reduced steady-state (SS) contraction. Furthermore, we determined whether the decrease in FSR was due to a decrease in sympathetic stimulation or enhanced parasympathetic signaling. In the RVT preparation, we found that the inhibitory effect of Lzm-S on FSR was prevented by NO synthase (NOS) inhibitors. A cGMP inhibitor also blocked the depressant activity of Lzm-S. However, in contrast to the Lzm-S-induced decline in SS contraction, chemical removal of the endocardial endothelium by Triton X-100 to eliminate endothelial NO release did not prevent the decrease in FSR. An inhibitory G protein was involved in the effect of Lzm-S, since FSR could be restored by treatment with pertussis toxin. Atropine prevented the Lzm-S-induced decline in FSR, whereas ₁- and ₂-adrenoceptor function was not impaired by Lzm-S. These results indicate that the Lzm-S-induced decrease in FSR results from a nonendothelial release of NO. NO then acts through inhibitory G protein to enhance parasympathetic signaling.

adrenergic -receptors; septic shock; myocardial depression; sympathetic response