ROLE OF NEUROPEPTIDE CGRP IN VASCULAR RESPONSE TO SEPSIS

神经肽 CGRP 在脓毒症血管反应中的作用

• 批准号: 3083328
• 负责人: WARWICK A ARDEN
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3083328
• 关键词: aorta; bacterial polysaccharides; calcitonin gene related peptide; capsaicin; cyclic AMP; cyclic GMP; disease /disorder model; endotoxins; enzyme activity; inhibitor /antagonist; laboratory rat; microcirculation; neuropeptides; nitric oxide; phosphodiesterase inhibitors; radioimmunoassay; tissue /cell culture; vascular endothelium; vascular resistance; vascular smooth muscle

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.

该建议的基本假设是降钙素基因相关 肽（CGRP）是一个重要的调解人的血管失调， 感染性休克的后期 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，显示在面对增加的一氧化氮（NO）增强的效力 由于血管cGMP和 cAMP系统。 本提案中所述的研究旨在： 1)进一步确定CGRP对细胞内的作用机制， 血管平滑肌，特别是， CGRP和另一种已知影响血管功能的介质之间的关系 在败血性休克期间，NO和2）确定是否有因果关系 血管周围CGRP释放增加与 感染性休克和进行性血管功能障碍