Nitric oxide inhibits the positive chronotropic and inotropic responses to sympathetic nerve stimulation in the isolated guinea-pig atria
Nitric oxide inhibits the positive chronotropic and inotropic responses to sympathetic nerve stimulation in the isolated guinea-pig atria
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DOI：
10.1016/s0165-1838(98)00173-8
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发表时间：
1999-02-15
期刊：
影响因子：
--
通讯作者：
Paterson, DJ
中科院分区：
文献类型：
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作者：
Choate, JK;Paterson, DJ
本研究旨在确定一氧化氮（NO）是否调节离体豚鼠双心房/右星状神经节对心脏交感神经刺激（SNS）的正性变时性和正性肌力反应。以1、2、3和5 Hz的恒定电压刺激神经节，测量心率或收缩力的变化。选择性神经元NO合酶（nNOS）抑制剂TRIM（1-（2-三氟甲基苯基）咪唑; 100 μ M）和7-NiNa（7-硝基吲唑的Na+盐：100 μ M）显著增强了对SNS的正性变时性和正性肌力反应。用非同种型选择性NOS抑制剂N ω硝基-L-精氨酸（L-NA; 100 μ M）观察到心率的类似结果，所有作用用L-精氨酸（1 mM）逆转。NO供体硝普钠（SNP：100 μ M）增加基线心率和收缩力，并减弱对SNS的正性变时性和变力性反应。SNP还降低了对浴用去甲肾上腺素（NA：1 μ M）的正变时性反应。相反，7-NiNa没有改变浴用NA（0.1或1 μ M）的心率增加。鸟苷酸环化酶抑制剂ODQ（10 μ M）增强（模拟nNOS抑制）和环GMP（鸟苷3 '：5'-环一磷酸）类似物8-Br-cGMP（8-溴鸟苷3 '：5'-环一磷酸：1 mM）减弱（模拟外源性NO）对SNS的正性肌力反应。总之，这些结果与内源性NO一致，由nNOS合成，抑制心脏SNS通过循环GMP依赖性途径引起的正性变时性和变力性反应。(C)1999 Elsevier Science B. V.保留所有权利。
This study was designed to determine whether nitric oxide (NO) modulates the positive chronotropic and inotropic tin 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 mu M) and 7-NiNa (Na+ salt of 7-nitroindazole: 100 mu M) 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 mu M) all effects were reversed with L-arginine (I mM). The NO donor sodium nitroprusside (SNP: 100 mu M) 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 mu M) In contrast, 7-NiNa did not alter the increase in heart rate with bath-applied NA (0.1 or 1 mu M). The guanylyl cyclase inhibitor ODQ (10 mu M) 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 rue consistent with endogenous NO, synthesized from nNOS, inhibiting the positive chronotropic and inotropic responses evoked by cardiac SNS via a cyclic GMP-dependent pathway. (C) 1999 Elsevier Science B.V. All rights reserved.