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）：基本的微血管过程被认为是与性别无关的，直到表明男性和女性对血流和血管张力的调节不同；尽管性别在代谢和体积稳态中很重要，但性别是否影响交换尚不清楚。冠状动脉交换适应运动训练的研究表明，基础渗透性 (Ps) 和 Ps 对血管扩张剂腺苷的反应均存在性别依赖性变化。 3 提出的目的是评估以下假设：性激素导致基础屏障特性和屏障对血管活性刺激的反应的一些（但不是全部）性别特异性差异。屏障功能将通过测量幼鱼肌肉和肠系膜小动脉和小静脉（高代谢与低代谢）的基础和刺激条件下的体积稳态、水力渗透性（Landis 技术）和蛋白质渗透性（显微荧光光度法）的基本决定因素来量化（高代谢与低代谢）。 <40 天）和成熟（>9 周）、激素限定的雄性和雌性大鼠。在 Aim I 中，将评估 4 组的基础功能，以评估性激素独立特性。由于初步研究表明通透性反应存在性别差异，Aim II 重点评估腺苷酸和鸟苷酸环化酶途径的功能，并评估血管磷酸二酯酶亚型 (PDE I-V) 的功能和分布，以定义 4 组中性别敏感的信号传导机制。在目标 III 中，将在有或没有性激素的情况下评估急性功能，以区分基因组和非基因组作用。将评估所有动物的性激素状态，重点关注性别特异性交换变化背后的细胞和分子机制。关于微血管屏障动态性质的这一基本信息对于了解健康男性和女性的容量和溶质稳态至关重要（恢复到 1g 前的症状；运动后的容量损失和恢复；月经周期和怀孕）和疾病（较高的体重）。男性休克患者的死亡率高于女性）。