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.

对呼吸功能的中心控制的明确理解是 阐明许多机制的先决条件 呼吸系统疾病。 一种或多种反射的激活已被使用 作为识别不同呼吸系统的方法之一 神经元池，建立它们与它们之间的功能互连 在这些途径中识别神经递质。 在此提案中， 心肺和颈动脉化学反射将被激活，并将 以下假设测试：1）刺激心肺 化学感受器诱导神经活性停止。 这么快 强大的反应需要同时参与以下 途径：（i）位于soltractus solitarius核中的神经元 （nts）被激活，这些神经元反过来刺激神经元 Botzinger-gomplex（BOTC）和尾腹呼吸神经元 通过兴奋性氨基酸（EAA）受体组（CVRG）。 激活 BOTC和CVRG-神经元会释放γ-氨基丁酸 （GABA）和/或甘氨酸腹腹呼吸神经元组 （rvrg）; （ii）NTS还抑制RVRG和前动物前复合物（前 BOTC），通过直接的GABA能和/或甘氨酸能预测。 网 上述途径激活的影响是 RVRG-神经元的抑制作用，这导致了伪造的停止 神经活动。 2）颈动脉化学感受器的刺激引起 神经活动的增加，这是通过 以下途径：化学感受器投影位点的投影， 位于NTS的合并子核中，激发了RVRG-NERONS 反过来，它激发了phren的神经元。 EAA受体位于 RVRG和Phrenic核介导了神经神经的增加 化学感受器刺激后的活性。 生成的数据 从这些调查中可能会提供更好的理解 呼吸道调节机制，最终将有助于 为许多呼吸系统疾病设计更好的治疗方法。