CARDIORESPIRATORY REGULATORY MECHANISMS

心肺调节机制

• 批准号: 6070337
• 负责人: HREDAY N. SAPRU
• 金额: $ 1.54万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6070337
• 关键词: carotid body; chemoreceptors; gamma aminobutyrate; glutamate receptor; glycine; laboratory rat; neuropharmacology; neuroregulation; neurotransmitter transport; phrenic nerve; pulmonary respiration; respiration regulatory center; respiratory reflex; solitary tract nucleus

A clear understanding of the central control of respiratory function is a prerequisite for unraveling the mechanisms involved in many respiratory diseases. Activation of one or more reflexes has been used as one of the approaches for the identification of different respiratory neuronal pools, establish functional interconnections between them and identify neurotransmitters in these pathways. In this proposal, cardiopulmonary and carotid chemoreflexes will be activated and the following hypotheses tested: 1) Stimulation of the cardiopulmonary chemoreceptors induces cessation of phrenic nerve activity. This rapid and powerful response requires simultaneous involvement of the following pathways: (i) The neurons located in the nucleus tractus solitarius (nTS) are activated, these neurons, in turn, stimulate the neurons in the Botzinger-complex (BotC) and caudal ventral respiratory neuronal group (cVRG) via excitatory amino acid (EAA) receptors. Activation of BotC- and cVRG-neurons results in the release of gamma-aminobutyric acid (GABA) and/or glycine in the rostral ventral respiratory neuronal group (rVRG); (ii) The nTS also inhibits rVRG and pre-Botzinger complex (Pre- BotC), via direct GABAergic and/or glycinergic projections. The net effect of the activation of the afore-mentioned pathways is the inhibition of rVRG-neurons, which results in the cessation of phrenic nerve activity. 2) The stimulation of carotid chemoreceptors elicits an increase in phrenic nerve activity which is mediated via the following pathways: a projection from the chemoreceptor projection site, located in the commissural subnucleus of nTS, excites the rVRG-neurons which, in turn, excite the phrenic neurons. EAA receptors located in the rVRG and phrenic nucleus mediate the increase in phrenic nerve activity following the chemoreceptor-stimulation. The data generated from these investigations is likely to provide a better understanding of respirat ory regulatory mechanisms and will eventually help in devising better methods of treatment for many respiratory disorders.

清楚地认识呼吸功能的中枢控制是 是解开许多问题所涉及的机制的先决条件 呼吸道疾病。 已使用一种或多种反射激活 作为识别不同呼吸道疾病的方法之一 神经元池，在它们之间建立功能互连 识别这些途径中的神经递质。 在这个提案中， 心肺和颈动脉化学反射将被激活， 测试了以下假设：1）刺激心肺 化学感受器诱导膈神经活动停止。 这种快速的 强有力的反应需要以下方面的同时参与 途径：（i）位于孤束核的神经元 （nTS）被激活，这些神经元反过来又刺激神经元 Botzinger 复合体 (BotC) 和尾腹呼吸神经元 组（cVRG）通过兴奋性氨基酸（EAA）受体。 激活 BotC 和 cVRG 神经元导致 γ-氨基丁酸的释放 (GABA) 和/或甘氨酸在头端腹侧呼吸神经元组中 （rVRG）； (ii) nTS 还抑制 rVRG 和前 Botzinger 复合物（Pre- BotC），通过直接 GABA 能和/或甘氨酸能预测。 网 上述途径激活的效果是 抑制 rVRG 神经元，从而导致膈神经停止 神经活动。 2）颈动脉化学感受器的刺激引起 膈神经活动的增加是通过 以下途径：化学感受器投射位点的投射， 位于 nTS 连合亚核，兴奋 rVRG 神经元 反过来，又会兴奋膈神经元。 EAA受体位于 rVRG和膈核介导膈神经的增加 化学感受器刺激后的活性。 生成的数据 这些调查可能会提供更好的了解 呼吸调节机制，最终将有助于 为许多呼吸系统疾病设计更好的治疗方法。