Mechanisms of systemic vasodilation by lysozyme-c in septic shock

作者：Gotes Jose; Kasian Krika; Jacobs Hans; Cheng Zhao Qin; Mink Steven N^*

来源：Journal of Applied Physiology, 2012, 112(4): 638-650.

DOI：10.1152/japplphysiol.00707.2011

• hypotension
• hydrogen peroxide signaling
• vascular smooth muscle
• ethyl gallate
• cardiovascular collapse

Gotes J, Kasian K, Jacobs H, Cheng ZQ, Mink SN. Mechanisms of systemic vasodilation by lysozyme-c in septic shock. J Appl Physiol 112: 638-650, 2012. First published November 17, 2011; doi: 10.1152/japplphysiol.00707.2011.-In septic shock (SS), cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme-c (Lzm-S), released from leukocytes, contributed to systemic vasodilation in a canine model of SS. We then delineated the pathway by which this occurs in a canine carotid artery organ bath preparation (CAP). We showed that Lzm-S could intrinsically generate hydrogen peroxide (H2O2) and that H2O2 subsequently reacted with endogenous catalase to form compound I, an oxidized form of catalase. In turn, compound I led to an increase in cyclic guanosine 3%26apos;,5%26apos;-monophosphate to produce vasodilation. However, it was not clear from previous studies whether it is necessary for Lzm-S to bind to the vasculature to cause vasodilation or, alternatively, whether the generation of H2O2 by Lzm-S in the surrounding medium is all that is required. We examined this question in the present study in which we used multiple preparations. In a partitioned CAP, we found that when we added Lzm-S to a partitioned space in which a semipermeable membrane prevented diffusion of Lzm-S to the carotid artery tissue, vasodilation still occurred because of diffusion of H2O2. On the other hand, we found that Lzm-S could accumulate within the vascular smooth muscle layer (VSML) after 7 h of SS in a canine model. We also determined that when Lzm-S was located in close proximity to vascular smooth muscle cells, it could generate H2O2 to produce lengthening in a human cell culture preparation. We conclude that there are two mechanisms by which Lzm-S can cause vasodilation in SS. In one instance, H2O2 generated by Lzm-S in plasma diffuses to the VSML to cause vasodilation. In a second mechanism, Lzm-S directly binds to the VSML, where it generates H2O2 to produce vasodilation.

• 出版日期2012-2