Choate J K, Paterson D J
University Laboratory of Physiology, Oxford, UK.
J Auton Nerv Syst. 1999 Feb 15;75(2-3):100-8. doi: 10.1016/s0165-1838(98)00173-8.
This study was designed to determine whether nitric oxide (NO) modulates the positive chronotropic and inotropic (in paced atria) responses to cardiac sympathetic nerve stimulation (SNS) in the isolated guinea-pig double atrial/right stellate ganglion preparation. The ganglion was stimulated at 1, 2, 3 and 5 Hz at constant voltage and the changes in heart rate or force of contraction were measured. The selective neuronal NO synthase (nNOS) inhibitors TRIM (1-(2-trifluoromethylphenyl) imidazole; 100 microM) and 7-NiNa (Na+ salt of 7-nitroindazole; 100 microM) significantly enhanced the positive chronotropic and inotropic responses to SNS. Similar results for heart rate were seen with the non-isoform-selective NOS inhibitor N(omega)nitro-L-arginine (L-NA; 100 microM). All effects were reversed with L-arginine (1 mM). The NO donor sodium nitroprusside (SNP; 100 microM) increased baseline heart rate and force of contraction, and attenuated the positive chronotropic and inotropic responses to SNS. SNP also decreased the positive chronotropic response to bath-applied noradrenaline (NA; 1 microM). In contrast, 7-NiNa did not alter the increase in heart rate with bath-applied NA (0.1 or 1 microM). The guanylyl cyclase inhibitor ODQ (10 microM) enhanced (mimicking nNOS inhibition) and the cyclic GMP (guanosine 3':5'-cyclic monophosphate) analogue 8-Br-cGMP (8-bromoguanosine 3':5'-cyclic monophosphate; 1 mM) attenuated (mimicking exogenous NO) the positive inotropic response to SNS. Taken together, these results are consistent with endogenous NO, synthesized from nNOS, inhibiting the positive chronotropic and inotropic responses evoked by cardiac SNS via a cyclic GMP-dependent pathway.
本研究旨在确定一氧化氮（NO）是否调节离体豚鼠双心房/右星状神经节标本中对心脏交感神经刺激（SNS）的正性变时和变力（在起搏心房中）反应。在恒定电压下以1、2、3和5Hz刺激神经节，并测量心率或收缩力的变化。选择性神经元型一氧化氮合酶（nNOS）抑制剂TRIM（1-(2-三氟甲基苯基)咪唑；100μM）和7-NiNa（7-硝基吲唑的钠盐；100μM）显著增强了对SNS的正性变时和变力反应。非亚型选择性一氧化氮合酶抑制剂N(ω)-硝基-L-精氨酸（L-NA；100μM）对心率也有类似结果。所有这些效应都被L-精氨酸（1mM）逆转。NO供体硝普钠（SNP；100μM）增加了基础心率和收缩力，并减弱了对SNS的正性变时和变力反应。SNP还降低了对浴加去甲肾上腺素（NA；1μM）的正性变时反应。相比之下，7-NiNa并未改变浴加NA（0.1或1μM）引起的心率增加。鸟苷酸环化酶抑制剂ODQ（10μM）增强了（模拟nNOS抑制），而环磷酸鸟苷（cGMP）类似物8-溴-cGMP（8-溴鸟苷3':5'-环磷酸；1mM）减弱了（模拟外源性NO）对SNS的正性变力反应。综上所述，这些结果与由nNOS合成的内源性NO通过环磷酸鸟苷依赖性途径抑制心脏SNS诱发的正性变时和变力反应一致。
