Microvascular Permeability and Sex

微血管通透性和性别

• 批准号: 6965259
• 负责人: VIRGINIA H HUXLEY
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6965259
• 关键词: age difference; arterioles; capillary; electrical conductance; enzyme activity; estrogens; gender difference; hormone regulation /control mechanism; immunocytochemistry; juvenile animal; laboratory rat; mesentery; microcirculation; phosphodiesterases; polymerase chain reaction; protein isoforms; protein transport; sex hormones; striated muscles; testosterone; vascular endothelium permeability; western blottings

DESCRIPTION (provided by applicant): Fundamental microvascular processes were assumed to be sex-independent of until it was shown that flow & vascular tone are regulated differently by men & women; whether sex influences exchange is not known in spite of its importance in metabolic and volume homeostasis. Studies of coronary exchange in adaptation to exercise training show sex-dependent changes in both basal permeability (Ps) and Ps responses to the vasodilator, adenosine. 3 Aims are proposed to evaluate the hypothesis that sex hormones contribute to some, but not all, sex-specific differences in basal barrier properties and responses of the barrier to vasoactive stimuli. Barrier function will be quantified from measures of the essential determinants of volume homeostasis, hydraulic permeability (Landis technique) and protein permeability (microspectrofluorometry) under basal and stimulated conditions in arterioles and venules of muscle and mesentery (high vs. low metabolism) from juvenile (<40 d) and mature (>9 wk), hormone-defined, male and female rats. In Aim I basal function in the 4 groups will be assessed to evaluate sex-hormone independent properties. As initial studies indicate sex-differences in permeability responses, Aim II evaluates function focusing on adenylyl and guanylyl cyclase pathways and evaluates the function and distribution of the vascular phosphodiesterase isoforms (PDE I-V) to define the sex-sensitive signaling mechanisms in the 4 groups. In Aim III acute function will be evaluated with and without sex hormones to distinguish between genomic and non-gemomic actions. Sex hormone status will be evaluated for all animals to focus on the cellular and molecular mechanisms underlying sex-specific changes in exchange. This fundamental information on the dynamic nature of the microvessel barrier is essential to understanding volume and solute homeostasis in males & females in health (pre-syncopy on return to 1g; volume loss and restoration with exercise; menstrual cycle & pregnancy) and disease (higher mortality of male than female shock patients).

描述（由申请人提供）：假定基本的微血管过程是与性别无关的，直到表明男性和女性对流量和血管张力的调节不同为止。尽管其在代谢和体积稳态中重要性的重要性，但性别影响是否不知道。在适应运动训练中的冠状动脉交换的研究表明，基础渗透性（PS）和PS对血管扩张剂腺苷的反应的变化。提出了3个目的，以评估性激素在基础屏障特性中有助于某些但不是全部性别的差异和对​​血管活性刺激的障碍的反应的假设。屏障功能将根据体积稳态的基本决定因素，液压渗透率（Landis技术）和蛋白质通透性（微光谱法）的基础和刺激条件下的肌肉和刺激条件下的蛋白质通透性（微光谱法）进行量化，从而量化屏障功能。雌鼠。在AIM I中，将评估这四个组中的基础功能，以评估性激素独立特性。当初步研究表明渗透率反应中的性别差异时，AIM II评估了关注腺苷酸和鸟叶烯基环酶途径的功能，并评估了4组中血管磷酸二酯酶同型（PDE I-V）的功能和分布，以定义4组中性敏感的信号机制。在AIM III中，将使用有或没有性激素的急性功能来区分基因组和非gemomomic作用。将对所有动物的性激素状态进行评估，以关注性别特异性变化的细胞和分子机制。有关微血管屏障的动态性质的基本信息对于了解男性和女性在健康中的体积和溶质稳态至关重要（返回1G返回前的同时副本；通过运动恢复的同时和恢复;月经周期和怀孕）和疾病（男性休克患者的死亡率更高）。