Lim Kyungjoon, Burke Sandra L, Moretti John-Luis, Head Geoffrey A
Neuropharmacology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Exp Physiol. 2015 Oct;100(10):1132-44. doi: 10.1113/EP085312.
What is the central question of this study? Is the elevated tonic renal nerve activity induced by chronic angiotensin administration mediated by recruitment or increased firing frequency and does this occur via stress, chemoreflex or baroreflex pathways? What is the main finding and its importance? Long-term angiotensin treatment in rabbits elevates renal sympathetic nerve activity by recruitment of previously silent fibres. This was similar to the effect of chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors. Modulation of sympathetic nerve activity involves control by the CNS of the amplitude of neural discharges, reflecting recruitment of neurons and their firing frequency. We tested whether elevated tonic renal sympathetic nerve activity (RSNA) induced by chronic angiotensin administration is mediated by recruitment or increased firing frequency and whether this is characteristic of the pattern observed with activation of stress, chemoreflex or baroreflex pathways. Conscious rabbits treated with angiotensin II for 12 weeks to increase blood pressure by 10-30% were subjected to stress (air jet), hypoxia (10% O2 + 3% CO2) and drug-induced changes in blood pressure to produce baroreflexes. Total RSNA and RSNA burst amplitude were scaled to 100 normalized units (n.u.) by the maximal response to smoke. After 12 weeks of treatment, blood pressure was 17% higher than baseline 68 ± 1 mmHg (P = 0.02). Compared with sham treatment, total RSNA and burst amplitude were +82% (P < 0.001) and 39% (P = 0.04) greater, but burst frequency was similar. Total RSNA increased during hypoxia (+38% from 4.9 ± 0.7 n.u.), owing to greater amplitude, but not frequency. Air-jet stress increased total RSNA (+44% from 4.3 ± 0.5 n.u.) and burst frequency (+21% from 5.4 ± 0.7 bursts s(-1) ), but not amplitude. Angiotensin enhanced total RSNA responses to both air jet (+33%) and hypoxia (+58%), but only increased the amplitude response to air jet. The RSNA baroreflexes reset to the higher blood pressure, but amplitude or frequency was not differentially altered. Chronic angiotensin treatment elevated RSNA by recruitment of neurons, which is similar to chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors.
本研究的核心问题是什么?慢性给予血管紧张素所诱导的肾神经紧张性活动增强是由神经纤维募集介导的,还是由放电频率增加介导的,以及这是通过应激、化学反射还是压力反射途径发生的?主要发现及其重要性是什么?对家兔进行长期血管紧张素治疗可通过募集先前沉默的纤维来提高肾交感神经活动。这与化学反射刺激的效果相似,但与应激或压力感受器激活的效果不同,表明血管紧张素激活的交感神经节前通路可能与化学感受器激活的通路相同。交感神经活动的调节涉及中枢神经系统对神经放电幅度的控制,这反映了神经元的募集及其放电频率。我们测试了慢性给予血管紧张素所诱导的肾交感神经紧张性活动(RSNA)增强是由神经纤维募集介导的,还是由放电频率增加介导的,以及这是否是应激、化学反射或压力反射通路激活所观察到模式的特征。用血管紧张素II治疗12周以使血压升高10 - 30%的清醒家兔接受应激(喷气)、低氧(10% O2 + 3% CO2)以及药物诱导的血压变化以产生压力反射。总RSNA和RSNA爆发幅度通过对烟雾的最大反应缩放到100个归一化单位(n.u.)。治疗12周后,血压比基线高17%,为68 ± 1 mmHg(P = 0.02)。与假手术治疗相比,总RSNA和爆发幅度分别增加了+82%(P < 0.001)和39%(P = 0.04),但爆发频率相似。低氧期间总RSNA增加(从4.9 ± 0.7 n.u.增加了+38%),这是由于幅度增大,而非频率增加。喷气应激使总RSNA增加(从4.3 ± 0.5 n.u.增加了+44%)以及爆发频率增加(从5.4 ± 0.7次/秒增加了+21%),但幅度未增加。血管紧张素增强了对喷气(+33%)和低氧(+58%)的总RSNA反应,但仅增加了对喷气的幅度反应。RSNA压力反射重置为更高的血压,但幅度或频率没有差异改变。慢性血管紧张素治疗通过募集神经元提高了RSNA,这与化学反射刺激相似,但与应激或压力感受器激活不同,表明血管紧张素激活的交感神经节前通路可能与化学感受器激活的通路相同。