NEUROMUSCULAR TRANSMISSION IN ARTERIES AND VEINS

描述：(改编自申请者的摘要)远程 这项提案中概述的研究目标是 阻容血管的神经控制机制 内脏循环和决定其基础的机制 这两个血管网络的不同调节。建议数 研究将比较交感神经在豚鼠中的共同传递 肠系膜动脉和静脉。PI假设对神经的反应 静脉和动脉刺激的不同之处在于：(1) 是由三磷酸腺苷和去甲肾上腺素(NE)在平滑肌中启动的不同 和/或(2)附近的ATP和NE的数量和/或比率 节后受体不同。具体目标1和2将涉及 这一假说的第一部分通过刻画外源效应 和内源性去甲肾上腺素和三磷酸腺苷对膜电位的影响(细胞内 微电极技术)和力量发展(器官浴 实验)，并确定是否不同 P2嘌呤能和α-肾上腺素能受体的亚型也参与其中。 具体目标3将通过以下方式解决这一假设的第二部分 使用最先进的技术同时测量神经 诱发的ATP流出(高效液相-荧光检测)和去甲肾上腺素(高效液相-荧光检测) 电化学检测)在动脉和静脉。因此，肠系膜动脉 和静脉将在两个发射器释放方面进行唯一的比较 以及节后效应机构。这些研究将提供新的 对神经对动脉和静脉的不同控制的洞察。 它们还有助于阐明三磷酸腺苷作为神经递质的作用。 在内脏环流中的作用及其与以NE为主的关系 交感神经递质。

DESCRIPTION: (adapted from the applicant's abstract) The long range objective of the research outlined in this proposal is to characterize neural control mechanisms of resistance and capacitance blood vessels of the splanchnic circulation and determine mechanisms which underlie differential regulation of these two vascular networks. The proposed studies will compare sympathetic co-transmission in guinea pig mesenteric artery and vein. The PI hypothesizes that responses to nerve stimulation in vein and artery differ because: (1) the mechanisms which are initiated by ATP and norepinephrine (NE) in smooth muscle differ and/or (2) the amount and/or ratio of ATP and NE at the vicinity of the postjunctional receptor differ. Specific Aims 1 and 2 will address the first part of this hypothesis by characterizing the effects of exogenous and endogenous NE and ATP on membrane potential (intracellular microelectrode techniques) and force development (organ bath experiments) in artery and vein and determining whether different subtypes of P2 purinergic and alpha-adrenergic receptors are involved. Specific Aim 3 will address the second part of this hypothesis by employing state-of-the-art techniques to simultaneously measure nerve evoked outflow of ATP (HPLC-fluorscence detection) and NE (HPLC- electrochemical detection) in artery and vein. Thus, mesenteric artery and vein will be uniquely compared in terms of both transmitter release and postjuctional effector mechanisms. These studies will provide new insights into the differential control of arteries and veins by nerves. They will also aid in clarifying the role of ATP as a neurotransmitter in the splanchnic circulation and its relationship to NE as the primary sympathetic neurotransmitter.