NEUROGENIC VASODILATION--MEDIATORS AND MECHANISMS

贯穿大脑循环的动脉有内在张力，这 是由仍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 降低这种基本音调的水平，这是一种 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 确定各个时刻的收缩状态。大脑皮层 流通在许多方面都是独一无二的。神经介导的血管扩张 是在这张床上发音的。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。 随着cAMP和cAMP水平的变化， 环状GMP。然而，脑血管运动的许多机制 控制还没有完全阐明。这样做的具体目的是 建议有：1)确定内皮依赖性 体动脉短暂的超极化是持续的。 由于大脑的固有特性，在大脑动脉中 还是血管平滑肌细胞的独特作用的结果 血管床中内皮源性超极化因子，2)至 揭示两种可能机制中的哪一种，钾电导增加 或增强的生电Na/K ATPase活性，是导致 脑动脉内皮依赖性超极化，3)至 建立旋回变化之间的时间关系 核苷酸水平和血管扩张，这将由激活引起 动脉周围神经以及非内皮细胞和内皮细胞- 依赖的扩张器和4)检验假设 血管内皮细胞对压力引起的脑动脉去极化的影响 而收缩取决于动脉的大小。以下是 将采用以下技术：1)连续测量直径 使用高分辨率视频对分离的大脑动脉进行加压 尺寸分析仪，2)动脉环上的等长力测量- 片段，3)膜电位的细胞内记录和4) 用放射免疫法测定环核苷酸含量。 决定脑血管的细胞机制的阐明 Tone将有助于更好地理解自动调节和 将与未来对血管病因学的研究相关 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.