Takita T, Ikeda J, Sekiguchi Y, Demachi J, Li S L, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Auton Nerv Syst. 1998 Jul 15;71(2-3):69-74. doi: 10.1016/s0165-1838(98)00071-x.
Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this study, we investigated whether inhibition of the L-arginine NO system augments the positive inotropic response of the left ventricle to direct stimulation of the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was infused into the left anterior descending (LAD) coronary artery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeated. We used the maximum of the first derivative of left ventricular pressure (LV max d P/dt) as an index of the myocardial contractility. Plasma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in five of twelve dogs. L-NAME treatment significantly augmented the inotropic response of the left ventricle (percent change in the LV max dP/dt) to LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supramaximal stimulation train did not change after L-NAME and L-arginine treatment. L-NAME significantly increased plasma norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plasma epinephrine concentration in the coronary sinus. It is concluded that the inhibition of the L-arginine NO system augmented the positive inotropic effect on the left ventricle during sympathetic nerve stimulation in normal dogs in vivo.
最近，有证据表明一氧化氮（NO）在体外和体内均能调节β-肾上腺素能刺激诱导的心肌收缩。在本研究中，我们调查了抑制L-精氨酸NO系统是否会增强犬体内左心室对交感神经直接刺激的正性肌力反应。对12只麻醉且切断迷走神经的犬，以次最大强度（5 V，2.5、5和10 Hz）和最大强度（10 V，10 Hz）对左星状神经节（LSG）进行1分钟的电刺激。接下来，在同一只犬中，将N（ω）-硝基-L-精氨酸甲酯（L-NAME）注入左前降支（LAD）冠状动脉，并按照相同方案重复LSG刺激。最后，将L-精氨酸注入LAD动脉，并重复LSG刺激。我们将左心室压力的一阶导数最大值（LV max dP/dt）用作心肌收缩力的指标。在12只犬中的5只中，于L-NAME治疗前后，在冠状窦测量血浆肾上腺素和去甲肾上腺素浓度。L-NAME治疗显著增强了左心室对LSG次最大刺激序列的正性肌力反应（LV max dP/dt的百分比变化），分别从164±13增至212±21（P<0.03），从187±15增至234±25（P<0.05），以及从220±19增至280±33%（P<0.05）。L-精氨酸治疗可逆转此反应。然而，L-NAME和L-精氨酸治疗后，对最大刺激序列的正性肌力反应未发生变化。L-NAME显著增加了冠状窦血浆去甲肾上腺素浓度，从0.69±0.41增至1.00±0.52 ng/ml，而血浆肾上腺素浓度未改变。结论是，在正常犬体内交感神经刺激期间，抑制L-精氨酸NO系统增强了对左心室的正性肌力作用。
