Li Yu-Long, Ding Yanfeng, Agnew Chad, Schultz Harold D
Dept. of Cellular and Integrative Physiology, Univ. of Nebraska Medical Center, Omaha, NE 68198, USA.
J Appl Physiol (1985). 2008 Sep;105(3):782-90. doi: 10.1152/japplphysiol.90533.2008. Epub 2008 Jun 26.
An enhancement of peripheral chemoreflex sensitivity contributes to sympathetic hyperactivity in chronic heart failure (CHF) rabbits. The enhanced chemoreflex function in CHF involves augmented carotid body (CB) chemoreceptor activity via upregulation of the angiotensin II (ANG II) type 1 (AT(1))-receptor pathway and downregulation of the neuronal nitric oxide synthase (nNOS)-nitric oxide (NO) pathway in the CB. Here we investigated whether exercise training (EXT) normalizes the enhanced peripheral chemoreflex function in CHF rabbits and possible mechanisms mediating this effect. EXT partially, but not fully, normalized the exaggerated baseline renal sympathetic nerve activity (RSNA) and the response of RSNA to hypoxia in CHF rabbits. EXT also decreased the baseline CB nerve single-fiber discharge (4.9 +/- 0.4 vs. 7.7 +/- 0.4 imp/s at Po(2) = 103 +/- 2.3 Torr) and the response to hypoxia (20.6 +/- 1.1 vs. 36.3 +/- 1.3 imp/s at Po(2) = 41 +/- 2.2 Torr) from CB chemoreceptors in CHF rabbits, which could be reversed by treatment of the CB with ANG II or a nNOS inhibitor. Our results also showed that NO concentration and protein expression of nNOS were increased in the CBs from EXT + CHF rabbits, compared with that in CHF rabbits. On the other hand, elevated ANG II concentration and AT(1)-receptor overexpression of the CBs in CHF state were blunted by EXT. These results indicate that EXT normalizes the CB chemoreflex in CHF by preventing an increase in afferent CB chemoreceptor activity. EXT reverses the alterations in the nNOS-NO and ANG II-AT(1)-receptor pathways in the CB responsible for chemoreceptor sensitization in CHF.
外周化学反射敏感性增强促成慢性心力衰竭（CHF）兔的交感神经过度活跃。CHF中化学反射功能增强涉及通过上调血管紧张素II（ANG II）1型（AT(1)）受体途径和下调颈动脉体（CB）中神经元型一氧化氮合酶（nNOS）-一氧化氮（NO）途径来增强CB化学感受器活性。在此，我们研究了运动训练（EXT）是否能使CHF兔增强的外周化学反射功能恢复正常以及介导此效应的可能机制。EXT部分但未完全使CHF兔夸大的基础肾交感神经活动（RSNA）以及RSNA对低氧的反应恢复正常。EXT还降低了CHF兔CB化学感受器的基础CB神经单纤维放电（在Po(2)=103±2.3 Torr时为4.9±0.4对7.7±0.4次/秒）以及对低氧的反应（在Po(2)=41±2.2 Torr时为20.6±1.1对36.3±1.3次/秒），用ANG II或nNOS抑制剂处理CB可使其逆转。我们的结果还表明，与CHF兔相比，EXT + CHF兔的CB中NO浓度和nNOS蛋白表达增加。另一方面，EXT使CHF状态下CB中升高的ANG II浓度和AT(1)受体过表达减弱。这些结果表明，EXT通过防止传入CB化学感受器活性增加使CHF中的CB化学反射恢复正常。EXT逆转了CB中负责CHF中化学感受器致敏的nNOS-NO和ANG II-AT(1)受体途径的改变。
