延髓头端腹外侧区一氧化氮对慢性心力衰竭大鼠心交感传入反射的影响

背景在慢性心力衰竭时,心交感传入反射的增强可能与心交感传入神经的敏感性增强以及中枢增益增强有关.已往实验证实慢性心力衰竭大鼠延髓头端腹外侧区一氧化氮生成减少导致刺激心交感传入神经引起的心交感传入反射增强.目的进一步探讨慢性心力衰竭大鼠延髓头端腹外侧区中的一氧化氮对化学物质刺激心脏引起的心交感传入反射的调控作用.设计随机对照实验.单位南京医科大学生理学系和美国内布拉斯加大学医学院生理学系.材料实验于2003-07/2004-05在南京医科大学生理学系完成.选用雄性SD大鼠56只,体质量360～420 g,随机分为慢性心力衰竭组和对照组,每组23只.方法慢性心力衰竭组应用去压力感受器神经支配的结扎冠状动脉诱发慢性心力衰竭,对照组行假手术,除不结扎冠状动脉外其余操作与慢性心力衰竭组相同.采用心室表面应用缓激肽(0.04μg和0.4μg)引起心交感传入反射以模拟慢性心力衰竭状态下心脏受到的化学刺激增强效应,记录应用缓激肽前后的血压和肾交感神经活动变化以评价心交感传入反射.行延髓头端腹外侧区插管,探讨微量注射药物对心交感传入反射的影响.主要观察指标①假手术和慢性心力衰竭大鼠的血流动力学、心脏重量和梗死面积.②假手术和慢性心力衰竭大鼠的心交感传入反射.③延髓头端腹外侧区注射一氧化氮合酶抑制剂MeTC对假手术和慢性心力衰竭大鼠的心交感传入反射的影响.④延髓头端腹外侧区注射一氧化氮供体SNAP对假手术和慢性心力衰竭大鼠的心交感传入反射的影响.⑤心室前壁表面应用利多卡因预处理对慢性心力衰竭大鼠心交感传入反射的影响.结果①在慢性心力衰竭大鼠,冠状动脉结扎引起(30.6±2.0)%的左心室壁梗死,收缩压、脉压、左室收缩期峰压和左心室压力最大变化速率明显降低,左室舒张末压明显增加.②与假手术大鼠相比,慢性心力衰竭大鼠的心交感传入反射显著增强.③延髓头端腹外侧区微量注射MeTC(80 nmol)仅增强假手术大鼠的心交感传入反射,对慢性心力衰竭大鼠的心交感传入反射无显著影响.④延髓头端腹外侧区微量注射SNAP(50 nmol)同时抑制假手术和慢性心力衰竭大鼠的心交感传入反射.⑤心室前壁表面用利多卡因预处理可完全抑制心室前壁表面应用缓激肽所引起的肾交感神经活动增加.结论延髓头端腹外侧区的一氧化氮抑制正常大鼠和慢性心力衰竭大鼠心室表面应用缓激肽引起的心交感传入反射,慢性心力衰竭大鼠心交感传入反射增强与延髓头端腹外侧区中内源性一氧化氮减少有关.

Effect of nitric oxide on rostral ventrolateral medulla modulating cardiac sympathetic afferent reflex in rats with chronic heart failure

BACKGROUND: Nitric oxide in the central nervous system is involved in controlling the sympathetic outflow. The authors' recent data show that the reduction of nitric oxide in the rostral ventrolateral medulla (RVLM)enhanced the cardiac sympathetic afferent reflex (CSAR) evoked by stimulating the cardiac sympathetic afferent nerves in rats with chronic heart failure (CHF).OBJECTIVE: To further investigate the effect of nitric oxide in the RVLM on modulating the CSAR evoked by epicardial chemical stimulation in rats with CHF.DESIGN: Randomized controlled experiment.SETTING: Department of Physiology, Nanjing Medical University, and Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine.MATERIALS: This study was carried out in the Department of Physiology, Nanjing Medical University from July 2003 to May 2004. A total of 52male Sprague-Dawley rats weighing 360-420 g were used, and were randomly divided into chronic heart failure group and control group with 23 in each group.METHODS: The rats were carried out either sham surgery or the left coronary artery ligation. Six to eight weeks later, all rats were anesthetized with α-chloralose and urethane and baroreceptor denervated and vagotomized. The CSAR was evoked by epicardial application of bradykinin (BK, 0.04 μg and 0.4 μg in 2.0 μL) to mimic the effect of chemical stimulation on the heart in the CHF state. The renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were recorded at baseline and during elicitation of the CSAR. Cannulae were inserted into the RVLM for microinjections.croinjection of MeTC, a nitric oxide synthase inhibitor, into the RVLM on Effects of epicardial pretreatment with lidocaine on the CSAR in CHF rats.infarction of (30.6±2.0) % of the left ventricular (LV) surface. The systolic arterial pressure, pulse pressure, left ventricle peak systolic pressure and maximum of the first differentiation of left ventricular pressure were decreased and the left ventricular end-diastolic pressure was significantly ininto the RVLM had no significant effects on the CSAR in rats with CHF,of SNAP (50 nmol) into the RVLM inhibited the CSAR in both sham rats ventricle abolished the CSAR evoked by epicardial application ofBK on the same area.CONCLUSION: Nitric oxide in the RVLM inhibits the CSAR evoked by epicardial application of BK in normal rats and CHF rats, and the reduction of nitric oxide in the RVLM led to the augmentation of the CSAR in CHF rats.