CGRP, NO, AND SEPSIS INDUCED MICROVASCULAR DYSFUNCTION

CGRP、NO 和脓毒症引起的微血管功能障碍

• 批准号: 6181158
• 负责人: WARWICK A ARDEN
• 金额: $ 9.95万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6181158
• 关键词: arterioles; blood vessel disorder; calcitonin gene related peptide; calcium flux; endotoxins; hemodynamics; laboratory rat; microcirculation; nitric oxide; tissue /cell culture; vascular resistance; vascular smooth muscle; video microscopy

DESCRIPTION: (Adapted from the applicant's abstract) The broad and long-term objectives of this proposal are to define the mechanisms of peripheral vascular and microvascular dysfunction in trauma, ischemia, and circulatory shock. The investigator focuses on the role of the potent vasoactive neuropeptide calcitonin gene-related peptide (CGRP) in resistant artery dysfunction in endotoxin-induced circulatory shock. The fundamental hypothesis to be addressed is that in vivo exposure of the vasculature to LPS results in release of CGRP from sensory nerve terminals, enervating the vasculature and that CGRP in combination with enhanced vascular NO production contributes to the observed vasodilatation and diminished resistance vascular responsiveness. This investigation has two principal inter-related objectives: 1) to further define the cellular mechanisms of action of CGRP on resistance artery smooth muscle cell and specifically define interactions between CGRP and NO; 2) to establish whether a cause and effect relationship exists between augmented perivascular CGRP release during septic shock and progressive microvascular dysfunction. These hypotheses and objectives will be subjected to a rigorous examination using a combination of methodologies including systemic hemodynamic recordings in anesthetized rats, in vivo video microscopy of the cremaster muscle microcirculation, assessment of the functional state of isolated cannulated cremaster arterioles, and digital fluorescence ratio imaging of vascular smooth muscle calcium responses in intact cremaster arterioles. These techniques will allow the investigator to determine whether changes in vascular responses correlate with changes in intracellular calcium-mediated directly or indirectly by CGRP and/or NO.

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