ENDOGENOUS AND EXOGENOUS NITRIC-OXIDE INHIBITS NOREPINEPHRINE RELEASE FROM RAT-HEART SYMPATHETIC-NERVES
ENDOGENOUS AND EXOGENOUS NITRIC-OXIDE INHIBITS NOREPINEPHRINE RELEASE FROM RAT-HEART SYMPATHETIC-NERVES
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DOI：
10.1161/01.res.77.4.841
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发表时间：
1995-10-01
影响因子：
20.1
通讯作者：
FORSTERMANN, U
中科院分区：
文献类型：
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作者：
SCHWARZ, P;DIEM, R;FORSTERMANN, U
本研究旨在阐明一氧化氮（NO）是否控制大鼠心脏交感神经的去甲肾上腺素（NE）释放。心脏在Langendorff模式下灌注Tyrode溶液。用1或3hz的电流刺激右交感神经，测量NE的释放。NO合成酶（NOS）抑制剂n- g -硝基- l -精氨酸（L-NNA）以浓度依赖性的方式促进诱导的NE释放。这种促进作用独立于灌注压力的增加，并被l -精氨酸而非d -精氨酸立体特异性逆转。另一种NOS抑制剂n - g -甲基- l-精氨酸也产生类似的NE释放增加。no供体化合物s -亚硝基-n -乙酰-d， l-青霉胺，在L-NNA存在下，以浓度依赖的方式恢复对NE释放的抑制。3- morpholinosydnon亚胺也有类似的抑制作用。结果表明，NE的释放受内源性NO的抑制。Western blot结果显示，心肌组织中存在神经元NOS I和内皮细胞NOS III。用低浓度的CHAPS洗涤剂灌注心脏会对内皮细胞造成功能性损伤，这可以通过灌注压力的增加和乙酰胆碱诱导的冠状动脉血管舒张向收缩的转化来证明。然而，CHAPS治疗并没有促进NE的释放（正如NOS抑制剂一样），L-NNA仍然增加了CHAPS治疗的心脏中NE的释放。双标记免疫荧光组织化学显示星状神经节细胞和心脏神经元NOS I免疫反应性，部分神经元酪氨酸羟化酶染色阳性。这些发现表明，NO主要在神经元中产生，控制着大鼠心脏中NE的释放。
This study was designed to elucidate whether nitric oxide (NO) controls norepinephrine (NE) release from sympathetic nerves of the rat heart. Hearts were perfused in the Langendorff mode with Tyrode's solution. The right sympathetic nerve was stimulated with trains of 1 or 3 Hz and NE release was measured. The NO synthase (NOS) inhibitor N-G-nitro-L-arginine (L-NNA) enhanced the evoked NE release in a concentration-dependent manner. This facilitation was independent of the increase in perfusion pressure and was stereospecifically reversed by L-arginine but not D-arginine. Another NOS inhibitor, N-G-methyl-L-arginine, produced a similar increase in NE release. The NO-donor compound S-nitroso-N-acetyl-D,L-penicillamine, added in the presence of L-NNA, restored the suppression of NE release in a concentration-dependent fashion. A similar suppression was achieved with 3-morpholinosydnonimine. These results demonstrated that NE release is under the inhibitory control of endogenous NO. Western blots demonstrated the presence of neuronal NOS I and endothelial NOS III in the hearts. Perfusion of the hearts with a low concentration of the detergent CHAPS produced functional damage of the endothelium, as evidenced by an increase in perfusion pressure and a conversion of the acetylcholine-induced coronary vasodilation to a constriction. However, CHAPS treatment did not produce a facilitation of NE release (as did the NOS inhibitors), and L-NNA still increased NE release in CHAPS-treated hearts. Double-labeling immunofluorescence histochemistry showed NOS I immunoreactivity in stellate ganglion cells and in neurons of the heart, some of which also stained positive for tyrosine hydroxylase. These findings suggest that NO, predominantly generated in neurons, controls NE release in the rat heart.