Wang W, Zucker I H
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198-4575, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):R751-6. doi: 10.1152/ajpregu.1996.271.3.R751.
It is well accepted that sympathetic tone is elevated in chronic heart failure (HF) and that the cardiac sympathetic afferent reflex is a sympathoexcitatory reflex. There have been no studies designed to examine the role of this reflex in control of sympathetic outflow in the HF state. In this study we tested the hypothesis that cardiac sympathetic afferent reflexes are enhanced in HF and are, therefore, capable of contributing to the increase in sympathetic outflow in this disease state. Ventricular pacing was carried out in 14 dogs until signs of HF were evident. Fourteen sham dogs served as controls. At the time of the acute experiment the dogs were anesthetized with alpha-chloralose. The hemodynamic [arterial pressure and heart rate (HR)] and renal sympathetic nerve activity (RSNA) responses to left ventricular epicardial application of two doses of bradykinin (BK) and capsaicin (Cap) were determined in the sinoaortic-denervated and vagotomized state. The MAP, RSNA, and HR responses to BK were greater in the HF group compared with the sham group. The RSNA response to BK (50 micrograms) in the HF group was significantly increased (34.0 +/- 5.9 vs. 11.5 +/- 4.2%, P < 0.05). The MAP, RSNA, and HR responses to Cap in the HF group were similar to the responses to BK. The RSNA response to Cap in the HF group was significantly increased (29.8 +/- 11.3 vs. 13.8 +/- 2.3% for 10 micrograms, P < 0.05 and 46.5 +/- 10.7 vs. 18.7 +/- 3.1% for 100 micrograms, P < 0.05). The cyclooxygenase blocker indomethacin (5 mg/kg i.v.) attenuated the reflex responses to BK in the HF group. These data suggest that the enhanced cardiac sympathetic afferent reflex to epicardial BK in HF appears to be mediated by altered levels of prostaglandin synthesis. Blockade of cardiac sympathetic afferents with topical lidocaine reduced baseline of RSNA significantly more in the HF state than in the normal state (-24.2 +/- 3.6 vs. -4.3 +/- 4.5%, P < 0.05). We conclude from these data that the cardiac sympathetic afferent reflex is sensitized in the HF state and speculate that this enhanced cardiac sympathetic afferent reflex may contribute to the sustained higher sympathetic tone in chronic HF.
人们普遍认为，慢性心力衰竭（HF）时交感神经张力升高，且心脏交感传入反射是一种交感兴奋反射。尚无研究旨在探讨该反射在HF状态下对交感神经输出控制中的作用。在本研究中，我们检验了以下假设：HF时心脏交感传入反射增强，因此能够促使该疾病状态下交感神经输出增加。对14只犬进行心室起搏，直至出现明显的HF体征。14只假手术犬作为对照。在急性实验时，用α-氯醛糖麻醉犬。在去窦主动脉神经和迷走神经状态下，测定左心室心外膜应用两剂缓激肽（BK）和辣椒素（Cap）后血流动力学[动脉压和心率（HR）]及肾交感神经活动（RSNA）反应。与假手术组相比，HF组对BK的平均动脉压（MAP）、RSNA和HR反应更大。HF组对BK（50微克）的RSNA反应显著增加（34.0±5.9%对11.5±4.2%，P<0.05）。HF组对Cap的MAP、RSNA和HR反应与对BK的反应相似。HF组对Cap的RSNA反应显著增加（10微克时为29.8±11.3%对13.8±2.3%，P<0.05；100微克时为46.5±10.7%对18.7±3.1%，P<0.05）。环氧化酶阻断剂吲哚美辛（5毫克/千克静脉注射）减弱了HF组对BK的反射反应。这些数据表明，HF时对心外膜BK增强的心脏交感传入反射似乎由前列腺素合成水平改变介导。在HF状态下，局部应用利多卡因阻断心脏交感传入神经比正常状态下更显著降低RSNA基线（-24.2±3.6%对-4.3±4.5%，P<0.05）。我们从这些数据得出结论，HF状态下心脏交感传入反射敏感化，并推测这种增强的心脏交感传入反射可能导致慢性HF中持续较高的交感神经张力。
