Chen H I, Hu C T
Department of Physiology, Tzu Chi College of Medicine, Hualien, Taiwan, Republic of China.
Am J Physiol. 1997 Oct;273(4):H1816-23. doi: 10.1152/ajpheart.1997.273.4.H1816.
Endogenous nitric oxide (NO) plays an important role in maintaining a vasodilator tone. In the present study, we compared the effects of NO blockade on the steady and pulsatile components of arterial hemodynamics between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto strain (WKY), 22-26 wk of age. In the first series of experiments, various doses (1-30 mg/kg i.v.) of N(G)-nitro-L-arginine methyl ester (L-NAME) were administered to block the NO release in anesthetized WKY and SHR. In both WKY and SHR, L-NAME caused a dose-dependent increase in arterial pressure (AP) with a decrease in heart rate (HR). The maximal effects of L-NAME on AP and HR occurred at a dose of 10 mg/kg. Both the AP increase and HR decrease were higher in SHR (AP, +38 +/- 4 mmHg; HR, -49 +/- 5 beats/min) than WKY (AP, +22 +/- 3 mmHg; HR, -33 +/- 5 beat/min). In other series, the technique of impedance spectral analysis was employed to investigate the effects of L-NAME (10 mg/kg i.v.) on the arterial hemodynamics. The aortic pressure and flow waves were recorded and subjected to Fourier transform for the analysis of impedance spectra. Both in WKY (n = 12) and in SHR (n = 12), L-NAME significantly increased AP and total peripheral resistance (TPR). The pulsatile and frequency-dependent hemodynamics including characteristic impedance, wave reflection, and ventricular work were only slightly altered. Despite higher resting values of AP and TPR in SHR (mean AP, 154 +/- 7 mmHg; mean TPR, 204 +/- 17 x 10(3) dyn x s x cm(-5)) than WKY (mean AP, 94 +/- 6 mmHg; mean TPR, 98 +/- 12 x 10(3) dyn x s x cm(-5)), the magnitudes of AP and TPR increments after NO blockade were significantly higher in SHR (AP, +37 +/- 3 mmHg; TPR, +124 +/- 16 x 10(3) dyn x s x cm(-5)) than in WKY (AP, +24 +/- 3 mmHg; TPR, +45 +/- 7 x 10(3) dyn x s x cm(-5)). The continuous formation of endogenous NO affects predominantly the AP and peripheral resistance in both WKY and SHR. The windkessel functions, such as impedance spectra, pulse-wave reflection, and ventricular work, are less affected after NO blockade. In addition, the effects of NO release on the AP and TPR appear to be enhanced in rats with established hypertension.
内源性一氧化氮（NO）在维持血管舒张张力方面发挥着重要作用。在本研究中，我们比较了在22 - 26周龄的自发性高血压大鼠（SHR）和正常血压的Wistar - Kyoto品系大鼠（WKY）中，NO阻断对动脉血流动力学的稳定和脉动成分的影响。在第一系列实验中，静脉注射不同剂量（1 - 30 mg/kg）的N(G)-硝基-L-精氨酸甲酯（L-NAME）以阻断麻醉的WKY和SHR中的NO释放。在WKY和SHR中，L-NAME均导致动脉压（AP）呈剂量依赖性升高，心率（HR）降低。L-NAME对AP和HR的最大作用出现在10 mg/kg的剂量。SHR中AP升高和HR降低的幅度（AP，+38±4 mmHg；HR，-49±5次/分钟）高于WKY（AP，+22±3 mmHg；HR，-33±5次/分钟）。在其他系列实验中，采用阻抗谱分析技术研究L-NAME（静脉注射10 mg/kg）对动脉血流动力学的影响。记录主动脉压力和血流波形，并进行傅里叶变换以分析阻抗谱。在WKY（n = 12）和SHR（n = 12）中，L-NAME均显著升高AP和总外周阻力（TPR）。包括特征阻抗、波反射和心室作功在内的脉动和频率依赖性血流动力学仅略有改变。尽管SHR中AP和TPR的静息值（平均AP，154±7 mmHg；平均TPR，204±17×10(3) dyn×s×cm(-5)）高于WKY（平均AP，94±6 mmHg；平均TPR，98±12×10(3) dyn×s×cm(-5)），但NO阻断后SHR中AP和TPR升高的幅度（AP，+37±3 mmHg；TPR，+124±16×10(3) dyn×s×cm(-5)）显著高于WKY（AP，+24±3 mmHg；TPR，+45±7×10(3) dyn×s×cm(-5)）。内源性NO的持续生成主要影响WKY和SHR中的AP和外周阻力。在NO阻断后，诸如阻抗谱、脉搏波反射和心室作功等风箱功能受影响较小。此外，在已建立高血压的大鼠中，NO释放对AP和TPR的影响似乎增强。
