Sears C E, Choate J K, Paterson D J
University Laboratory of Physiology, Oxford, UK.
J Auton Nerv Syst. 1998 Aug 27;73(1):63-73. doi: 10.1016/s0165-1838(98)00123-4.
The role of nitric oxide (NO) in the sympatho-vagal control of heart rate was investigated in the cardiac sympathectomized and vagotomized anaesthetised rabbit and in the isolated guinea-pig atria with intact vagus nerve. Specific inhibition of neuronal nitric oxide synthase (nNOS) with 1-(2-trimethylphenyl) imidazole (TRIM, 50 mg kg(-1) i.v. in vivo) significantly enhanced the magnitude of the change in heart rate (HR) with sympathetic nerve stimulation (SNS, 31.6+/-4.5 bpm control vs. 49.7+/-6.0 bpm in TRIM, P < 0.05, 10 Hz). This effect was reversed by L-arginine (deltaHR 37.2+/-4.1 bpm, 50 mg kg(-1) i.v.). An enhanced HR response to SNS was also seen with the non-isoform specific inhibitor, N-omega-nitro-L-arginine (L-NA, 50 mg kg(-1) i.v.). Infusing isoprenaline (0.2 microg kg(-1) min(-1)) did not mimic the change in HR response to SNS with TRIM. There was, however, no significant effect of inhibition of NOS with TRIM L-NA or NG-monomethyl-L-arginine (L-NMMA, 20 mg kg(-1) i.v.) on the magnitude of the change in HR with vagal nerve stimulation (5 Hz) in vivo. There was also no significant effect of NOS inhibition on the change in HR with vagal nerve stimulation in vivo in the presence of pre-adrenergic stimulation or in the presence of propranolol (0.5 mg kg(-1) i.v., 2, 5 and 10 Hz stimulation). This result was confirmed in the isolated guinea-pig atria with the specific nNOS inhibitor, 7-nitroindazole (7-NiNa, 100 microM) at 1, 2, 3 or 5 Hz stimulation frequency. Our data suggest that endogenous NO plays an inhibitory role in cardiac sympathetic neurotransmission, but there was no convincing evidence from our results for a major role for endogenous NO in vagal control of heart rate, with or without prior adrenergic stimulation.
在心脏交感神经切除和迷走神经切断的麻醉兔以及迷走神经完整的离体豚鼠心房中，研究了一氧化氮（NO）在心率交感 - 迷走控制中的作用。用1 - （2 - 三甲基苯基）咪唑（TRIM，50 mg kg⁻¹静脉注射，体内）特异性抑制神经元型一氧化氮合酶（nNOS），可显著增强交感神经刺激（SNS，10 Hz）时心率（HR）变化的幅度（对照时HR变化为31.6±4.5次/分钟，TRIM处理后为49.7±6.0次/分钟，P < 0.05）。L - 精氨酸可逆转此效应（HR变化为37.2±4.1次/分钟，50 mg kg⁻¹静脉注射）。非异构体特异性抑制剂N - ω - 硝基 - L - 精氨酸（L - NA，50 mg kg⁻¹静脉注射）也可使对SNS的HR反应增强。静脉输注异丙肾上腺素（0.2 μg kg⁻¹ min⁻¹）不能模拟TRIM处理后对SNS的HR反应变化。然而，用TRIM、L - NA或NG - 单甲基 - L - 精氨酸（L - NMMA，20 mg kg⁻¹静脉注射）抑制NOS，对体内迷走神经刺激（5 Hz）时HR变化的幅度无显著影响。在肾上腺素能刺激前或存在普萘洛尔（0.5 mg kg⁻¹静脉注射，2、5和10 Hz刺激）的情况下，抑制NOS对体内迷走神经刺激时的HR变化也无显著影响。在离体豚鼠心房中，用特异性nNOS抑制剂7 - 硝基吲唑（7 - NiNa，100 μM），在1、2、3或5 Hz刺激频率下，也证实了这一结果。我们的数据表明，内源性NO在心脏交感神经传递中起抑制作用，但我们的结果没有令人信服的证据表明内源性NO在有或无先前肾上腺素能刺激的情况下，在迷走神经对心率的控制中起主要作用。
