NEUROGENIC VASODILATION--MEDIATORS AND MECHANISMS

明显的神经源性血管扩张，由非交感神经介导 从中枢神经系统流出，发生在大脑和 许多物种的脑外头循环。在猫身上， 乙酰胆碱和血管活性肠肽(VIP) 在这些神经扩张系统中有很强的传递性。 然而，包含神经的特定来源和分布 乙酰胆碱和血管活性肠肽的测定范围有限。 胆碱能神经元和突触后神经元之间可能存在突触前后的相互作用 在这些系统重叠的部位，Viper能神经流出，并且 它们导致其影响的机制尚未阐明。一个 神经源性血管扩张剂行为的频谱，范围从完全 阿托品对阿托品敏感对阿托品完全耐药，存在不同 取自猫、大鼠和兔子的头部血管。在这 建议，这些物种的动脉已经被选择来允许，通过 比较它们的扩张器特性、角色分离和 乙酰胆碱与血管活性肠肽的相互作用。这项研究的具体目的 主要内容包括：(1)详细研究了古生物的起源和分布 老年人头循环中的胆碱能和血管周围神经 并将这些发现与之前的观察结果在 猫，(2)突触前相互作用的评估 乙酰胆碱和血管活性肠肽对其血管周围释放的影响 猫和兔的神经，以及(3)血管平滑的测量 肌细胞电生理与神经源性血管扩张相关。 将采用以下技术：(1)胆碱的测量 乙酰转移酶活性，(2)免疫组织化学观察 含血管活性肠肽的血管周围神经和细胞(3)血管活性肠肽的测定 用放射免疫法测定血管活性肠肽从动脉样本中的含量和释放 (4)组织负荷后乙酰胆碱释放的估计 标记前体；(5)血管平滑的细胞内记录 利用微电极测量肌膜电位。这些研究将 提供有关神经源性疾病发生机制的新信息矩阵 血管扩张，有助于阐明一种血管的功能意义 神经支配涉及两个扩张器递质，并有助于 对正常状态下声调神经调节的认识 与大脑等病理情况有关的血管床 脑梗塞、缺血和血管性头痛；这反过来可能导致 这类疾病的药物管理的新战略。

Pronounced neurogenic vasodilation, mediated by non-sympathetic neural outflow from the central nervous system, occurs in both the cerebral and extracerebral cephalic circulation in a number of species. In the cat, acetylcholine and vasoactive intestinal polypeptide (VIP) havve been strongly implicated as transmitters in these neurodilating systems. However, the specific origins and distribution of nerves which contain acetylcholine and VIP have been determined only to a limited extent. Likely pre- and post-synaptic interactions between the cholinergic and VIPergic neural outflow at sites where these systems overlap, and the mechanisms whereby they cause their effects, have not been elucidated. A spectrum of neurogenic vasodilator behavior, ranging from fully atropine-sensitive to completely atropine-resistant, exists in different cephalic blood vessels taken from the cat, rat, and rabbit. In this proposal, arteries from these species have been selected to permit, by comparison of their dilator characteristics, separation of the roles and interactions of acetylcholine and VIP. The specific aims of this study include: (1) a detailed study of the origin and distribution of cholinergic and VIPergic perivascular nerves in the cephalic circulation of the rat and a comparison of these findings with previous observations in the cat, (2) an evaluation of presynaptic interactions between acetylcholine and VIP which may influence their release from perivascular nerves in the cat and rabbit, and (3) measurement of the vascular smooth muscle cell electrophysiological correlates of neurogenic vasodilation. The following techniques will be employed: (1) measurements of choline acetyltransferase activity, (2) immunohistochemical observation of VIP-containing perivascular nerves and cells, (3) determinations of VIP content and release from arterial samples using a radioimmunoassay for VIP, (4) estimates of acetylcholine release following tissue loading with a labeled precursor, and (5) intracellular recording of vascular smooth muscle membrane potential using microelectrodes. These studies will provide a matrix of new information about the mechanisms of neurogenic vasodilation, help clarify the functional significance of a type of innervation which involves two dilator transmitters, and contribute to an understanding of the neural regulation of tone under normal conditions in vascular beds which are involved in such pathological conditions as cerebal infarction and ischemia and vascular headache; this in turn, could lead to new strategies for pharmacological management of such diseases.