NEUROPEPTIDE CGRP AND VASCULAR RESPONSE TO SEPSIS

这一建议的基本假设是降钙素基因与 降钙素基因相关肽(CGRP)是血管松弛的重要介质 败血症休克的后期。此外，物质的影响 例如至少部分依赖于血管平滑肌CGRP 环磷酸腺苷(CAMP)的产生作为一种机制 行动，在一氧化氮(NO)增加的情况下显示出更强的效力 由于血管cGMP和cGMP之间的特定相互作用而产生 集中营系统。本提案中描述的研究旨在； 1)进一步明确CGRP在细胞内的作用机制 血管平滑肌和，具体地说，定义相互作用 降钙素基因相关肽与另一种已知影响血管功能的介质之间的关系 在感染性休克期间，NO和2)以确定是否有因果关系 血管周围降钙素基因相关肽释放增加 感染性休克和进行性血管功能障碍。

The basic hypothesis of this proposal is that Calcitonin Gene Related Peptide (CGRP) is an important mediator of vascular deregulation during the latter stages of septic shock. Moreover the effect of substances such as CGRP which rely, at least in part, on vascular smooth muscle cyclic adenosine monophosphate (cAMP) generation as a mechanism of action, show enhanced potency in the face of increased nitric oxide (NO) production due to a specific interaction between the vascular cGMP and cAMP systems. The studies described in this proposal are designed to; 1) further define the intracellular mechanisms of action of CGRP on vascular smooth muscle and, specifically, to define the interactions between CGRP and another mediator known to impact on vascular function during septic shock, NO and 2) to establish if a cause and effect relationship exists between augmented perivascular CGRP release during septic shock, and progressive vascular dysfunction.