NEUROMUSCULAR TRANSMISSION IN ARTERIES AND VEINS

描述：（改编自申请人的摘要） 本提案中概述的研究目标是描述 血管阻力和电容的神经控制机制 的内脏循环，并确定机制， 这两个血管网络的差异调节。拟议 研究将比较豚鼠的交感神经共传递 肠系膜动、静脉PI假设对神经的反应 静脉和动脉中的刺激不同，因为：（1） 由ATP和去甲肾上腺素（NE）在平滑肌中启动， 和/或（2）在所述区域附近的ATP和NE的量和/或比率， 连接后受体不同。具体目标1和2将解决 这一假设的第一部分，通过描述外源性的影响， 内源性NE和ATP对细胞膜电位的影响 微电极技术）和力发展（器官浴 实验）中，并确定是否不同 涉及P2嘌呤能和α-肾上腺素能受体的亚型。 具体目标3将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（HPLC-荧光检测）和NE流出（HPLC-荧光检测） 电化学检测）。肠系膜动脉 和静脉将在两个发射器释放方面进行独特的比较 和接合后效应器机制。这些研究将提供新的 深入了解神经对动脉和静脉的不同控制。 他们还将有助于澄清ATP作为神经递质的作用 内脏循环及其与NE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.