Picker O, Scheeren T W, Arndt J O
Department of Experimental Anesthesiology, Heinrich-Heine University, Düsseldorf, Germany.
Basic Res Cardiol. 2001 Jul;96(4):395-404. doi: 10.1007/s003950170048.
Nitric oxide synthase (NOS) inhibitors elicit bradycardias independent of the endothelium (e-NOS) or increases in blood pressure. Therefore, this bradycardia could be mediated by other NOS isoforms, most likely that of the nervous system (n-NOS). If so, heart rate variability (HRV) as a measure of vagal activity should be an indicator of the activity of n-NOS in vagal neurons. To test this, we studied the dose-effect relations of L-NAME (0.3 - 50 mg x kg(-1)) on heart rate (HR), HRV and systemic vascular resistance (SVR) in seven awake dogs. HRV was analyzed in the time domain as standard deviation of the RR-intervals (SDNN) and in the frequency domain as power in the high (0.15 - 0.5 Hz) and low (0.04 - 0.15 Hz) frequency range. The effects of HR and SDNN reached their maxima at a dose of 3 mg x kg(-1) and had their ED50 at 0.27 +/- 0.03 mg x kg(-1) and 0.43 +/- 0.1 mg x kg(-1), respectively, whereas SVR had its maximum at 10 mg x kg(-1) and ED50 at 0.86 +/- 0.11 mg x kg(-1) (p < 0.05). HF-power (vagal activity) predominated compared to LF-power (mainly sympathetic activity) during baseline as well as after L-NAME. The effects on HR and HRV were absent after ganglionic blockade (hexamethonium), whereas the effects on SVR remained unchanged. Thus, NO exerts a powerful restraining activity on vagal neurons and plays a key role in the adjustment of heart rate in awake resting animals with prevailing vagal activity.
一氧化氮合酶（NOS）抑制剂可引发与内皮无关的心动过缓（e-NOS）或血压升高。因此，这种心动过缓可能由其他NOS亚型介导，最有可能是神经系统的（n-NOS）。如果是这样，作为迷走神经活动指标的心率变异性（HRV）应该是迷走神经神经元中n-NOS活性的指标。为了验证这一点，我们研究了L-NAME（0.3 - 50 mg·kg⁻¹）对7只清醒犬的心率（HR）、HRV和全身血管阻力（SVR）的剂量效应关系。HRV在时域中分析为RR间期的标准差（SDNN），在频域中分析为高频率（0.15 - 0.5 Hz）和低频率（0.04 - 0.15 Hz）范围内的功率。HR和SDNN的效应在剂量为3 mg·kg⁻¹时达到最大值，其ED50分别为0.27±0.03 mg·kg⁻¹和0.43±0.1 mg·kg⁻¹，而SVR在10 mg·kg⁻¹时达到最大值，ED50为0.86±0.11 mg·kg⁻¹（p < 0.05）。在基线期以及给予L-NAME后，高频功率（迷走神经活动）相比于低频功率（主要是交感神经活动）占主导。在神经节阻断（六甲铵）后，对HR和HRV的效应消失，而对SVR的效应保持不变。因此，NO对迷走神经神经元具有强大的抑制作用，并且在迷走神经活动占主导的清醒静息动物的心率调节中起关键作用。
