NEUROGENIC VASODILATION--MEDIATORS AND MECHANISMS

整个脑循环的动脉具有固有张力， 是由尚未明确定义的机制产生的。 脑血流量的自动调节是通过增加或 降低基础音调的水平， 各种收缩和扩张影响，包括内皮 衍生物质、组织代谢物和血管周围神经， 决定每时每刻的收缩状态。 脑 流通在许多方面都是独一无二的。 神经介导的血管舒张 在这张床上很明显 内皮依赖性收缩和 这些动脉的扩张与大的、持续的变化有关 在膜电位和环磷酸腺苷水平的变化， 环GMP。 然而，脑血管扩张的许多机制 控制尚未完全阐明。 具体目标是 建议是：1）确定是否内皮依赖性 在体动脉中短暂的超极化持续存在 由于大脑动脉的固有特性， 血管平滑肌细胞或血管平滑肌细胞的独特作用的结果， 内皮衍生的超极化因子，2） 揭示两种可能机制中的哪一种，增加钾电导率 或增强的产电Na/K ATP酶活性，负责 脑动脉内皮依赖性超极化，3） 建立周期性变化之间的时间关系 核苷酸水平和血管舒张，这将引起激活 动脉周围神经和内皮非依赖性和内皮- 依赖性扩张剂和4）测试的假设， 内皮细胞对压力诱导的脑动脉去极化的影响 收缩取决于动脉的大小 以下 将采用以下技术：1）连续直径测量， 使用高分辨率视频分离加压脑动脉 尺寸分析仪，2）动脉环上的等距力测量- 节段，3）膜电位的细胞内记录和4） 通过放射免疫测定法测定环核苷酸含量。 阐明决定脑血管疾病的细胞机制 音调将有助于更好地理解自动调节， 将与未来的血管性心脏病病因学研究相关， 高血压、血管痉挛和血管性头痛等疾病。

Arteries throughout the cerebral circulation have intrinsic tone, which is generated by mechanisms that are still not well-defined. Autoregulation of cerebral blood flow is accomplished by increasing or decreasing the level of this basal tone and it is the interplay of a variety of constrictor and dilator influences, including endothelial derived substances, tissue metabolites and perivascular nerves that determine the contractile state from moment to moment. The cerebral circulation is unique in many respects. Neurally mediated vasodilation is pronounced in this bed. Endothelium-dependent constriction and dilation of these arteries are associated with large, sustained changes in membrane potential and with changes in levels of both cyclic AMP and cyclic GMP. However, many of the mechanisms of cerebral vasomotor control have not yet been fully elucidated. The specific aims of this proposal are: 1) to determine whether endothelium-dependent hyperpolarization, which is transient in systemic arteries, is sustained in cerebral arteries due to intrinsic properties of the cerebral vascular smooth muscle cells or is a result of unique actions of the endothelium-derived hyperpolarizing factor in this vascular bed, 2) to reveal which of two probable mechanisms, increased potassium conductance or enhanced electrogenic Na/K ATPase activity, is responsible for endothelium-dependent hyperpolarization in cerebral arteries, 3) to establish the temporal relationship between alterations in cyclic nucleotide levels and vasodilation, which will be evoked by activation of periarterial nerves and by endothelium-independent and endothelium- dependent dilators and 4) to test the hypothesis that the contribution of the endothelium to pressure-induced cerebral arterial depolarization and constriction is dependent on arterial size. The following techniques will be employed: 1) continuous diameter measurements on isolated, pressurized cerebral arteries using a high resolution video dimension analyzer, 2) isometric force measurements on arterial ring- segments, 3) intracellular recordings of membrane potential and 4) measurement of cyclic nucleotide content by radioimmunoassay. Elucidation of the cellular mechanisms that determine cerebrovascular tone will contribute to a better understanding of autoregulation and will be relevant to future investigations of the etiology of vascular diseases such as hypertension, vasospasm and vascular headache.