Kolo Lacy L, Westfall Thomas C, Macarthur Heather
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
Am J Physiol Heart Circ Physiol. 2004 Jan;286(1):H296-303. doi: 10.1152/ajpheart.00668.2003.
Nitric oxide (NO) reacts with catecholamines resulting in their deactivation. In this study, we demonstrated that coincubation of NO donors with sympathetic neurotransmitters decreased the amount of norepinephrine detected but not ATP or neuropeptide Y (NPY). Furthermore, we found that the ability of norepinephrine to increase perfusion pressure in the isolated perfused mesenteric arterial bed of the rat was attenuated by the incubation of norepinephrine with the NO donor diethylamine NONOate. Conversely, the vasoconstrictive ability of NPY and ATP was unaffected by incubation with NONOate. Periarterial nerve stimulation in the presence of the NO synthase (NOS) inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) resulted in an increase in both perfusion pressure response and norepinephrine levels. This was prevented by l-arginine, demonstrating that the effects of l-NAME were indeed specific to the inhibition of NOS. To confirm that NO was not altering the release of norepinephrine from the sympathetic nerve via presynaptic activation of guanylate cyclase, we repeated the experiments in the presence of the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxaloine-one (ODQ). Unlike l-NAME, ODQ infusion did not increase norepinephrine overflow, demonstrating that modulation of norepinephrine by NO at the vascular neuroeffector junction of the rat mesenteric vascular bed is not the result of presynaptic guanylate cyclase activation. These results demonstrate that, in addition to being a direct vasodilatator, NO can also alter vascular reactivity at the sympathetic neuroeffector junction in the rat mesenteric bed by deactivating the vasoconstrictor norepinephrine.
一氧化氮（NO）与儿茶酚胺发生反应，导致其失活。在本研究中，我们证明了将NO供体与交感神经递质共同孵育会减少检测到的去甲肾上腺素量，但不会减少ATP或神经肽Y（NPY）的量。此外，我们发现，在大鼠离体灌注肠系膜动脉床中，去甲肾上腺素与NO供体二乙胺NONOate孵育后，其增加灌注压力的能力减弱。相反，NPY和ATP的血管收缩能力不受与NONOate孵育的影响。在存在一氧化氮合酶（NOS）抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）的情况下进行动脉周围神经刺激，会导致灌注压力反应和去甲肾上腺素水平均升高。L-精氨酸可阻止这种情况，表明L-NAME的作用确实是特异性抑制NOS。为了证实NO不是通过鸟苷酸环化酶的突触前激活来改变交感神经释放去甲肾上腺素，我们在存在鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3-a]-喹喔啉-1（ODQ）的情况下重复了实验。与L-NAME不同，输注ODQ不会增加去甲肾上腺素的溢出，这表明在大鼠肠系膜血管床的血管神经效应器连接处，NO对去甲肾上腺素的调节不是突触前鸟苷酸环化酶激活的结果。这些结果表明，除了作为直接血管舒张剂外，NO还可通过使血管收缩剂去甲肾上腺素失活，改变大鼠肠系膜床交感神经效应器连接处的血管反应性。
