Chronic inhibition of endothelial nitric oxide synthase activity in nucleus tractus solitarii enhances baroreceptor reflex in conscious rats
Chronic inhibition of endothelial nitric oxide synthase activity in nucleus tractus solitarii enhances baroreceptor reflex in conscious rats
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慢性抑制孤束核内皮一氧化氮合酶活性可增强清醒大鼠的压力感受器反射
DOI：
10.1113/jphysiol.2002.030270
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
J. Paton
中科院分区：
文献类型：
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作者：
H. Waki;S. Kasparov;Liang;D. Murphy;Tsuyoshi Shimizu;J. Paton
在急性实验中，我们先前证明，一氧化氮(NO)供体外源性应用于孤束核(NTS)可抑制压力感受性心脏反射。在这项研究中，我们确定了内源性内皮型一氧化氮合酶(ENOS)活性在慢性调节清醒大鼠压力感受器反射功能中的作用。将指导表达截短eNOS的重组腺病毒载体显微注射到NTS，以抑制内源性eNOS的活性。用无线电遥测的方法连续监测自由活动动物的动脉压，用时间序列方法测定自发性压力感受器反射增益(SBRG)。自基因转导后第7天至第21天，SBRG逐渐升高，第21天时(1.68±0.20ms−1，n=6)显著高于基因转导前(1.13±0.09ms)−1，P<；0.001。该值也显著高于正常对照组(1.04±0.21ms−1；n=6)和生理盐水组(1.12±0.15ms−1；n=4，P<0.05)。此外，心率从336±6降至318±8b.pm。(P<；0.05)转基因后21天。这一数值也显著低于对照组(EGFP：348±9 b.pm，n=6，P<0.01；生理盐水：347±5 b.pm，n=4，P<0.05)。基因转移不影响动脉压。这些发现表明，在清醒的大鼠中，eNOS在NTS内是结构性活跃的，是调节压力感受器反射增益和心率的一个因素。
In acute experiments, we demonstrated previously that nitric oxide (NO) donors exogenously applied to the nucleus tractus solitarii (NTS) depressed the baroreceptor cardiac reflex. In this study, we determined a role for endogenous endothelial nitric oxide synthase (eNOS) activity in the NTS for chronically regulating baroreceptor reflex function in conscious rats. A recombinant adenoviral vector directing expression of a truncated form of eNOS was microinjected bilaterally into the NTS to inhibit endogenous eNOS activity. Arterial pressure was monitored continuously using radio‐telemetry in freely moving animals and spontaneous baroreceptor reflex gain (sBRG) determined by a time‐series method. sBRG showed a gradual increase from day 7 to 21 after gene transfer and the value at day 21 (1.68 ± 0.20 ms mmHg−1, n= 6) was significantly higher than that before gene transfer (1.13 ± 0.09 ms mmHg−1, P < 0.001). This value was also significantly higher than that in rats in which enhanced green fluorescent protein (eGFP) was expressed in the NTS (1.04 ± 0.21 ms mmHg−1; n= 6, P < 0.01) and saline‐treated groups (1.12 ± 0.15 ms mmHg−1; n= 4, P < 0.05), which did not change from control levels. In addition, heart rate decreased from 336 ± 6 to 318 ± 8 b.p.m. (P < 0.05) 21 days after gene transfer. This value was also significantly lower than that in control groups (eGFP: 348 ± 9 b.p.m., n= 6, P < 0.01; saline: 347 ± 5 b.p.m., n= 4, P < 0.05). Gene transfer did not affect arterial pressure. These findings suggest that in the conscious rat eNOS is constitutively active within the NTS and is a factor regulating baroreceptor reflex gain and heart rate.