Neuronal nitric-oxide synthase inhibition facilitates adrenergic neurotransmission in rat mesenteric resistance arteries
Neuronal nitric-oxide synthase inhibition facilitates adrenergic neurotransmission in rat mesenteric resistance arteries
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DOI：
10.1124/jpet.105.094656
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发表时间：
2006-02-01
影响因子：
3.5
通讯作者：
Kawasaki, H
中科院分区：
文献类型：
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作者：
Hatanaka, Y;Hobara, N;Kawasaki, H
在去内皮的大鼠肠系膜血管灌流床上，观察了非选择性一氧化氮合酶抑制剂[L精氨酸甲酯和L精氨酸]和特异性一氧化氮合酶抑制剂[乙烯基-L-N-5-(1-亚氨基-3-丁烯基)-L-鸟氨酸]对肾上腺素能神经介导的血管收缩的影响。灌流L-NAME、L-NNA或L-VNIO可明显增强刺激动脉周围神经(PNS；2-8 Hz)引起的血管收缩反应，而不影响外源性注射去甲肾上腺素(NE)引起的血管收缩反应。加入合成一氧化氮(NO)的前体L-精氨酸，可翻转L-NAME对三叉神经核反应的增强作用。灌流8 Hz三七总皂苷可增加灌流液中NE的释放。在辣椒素[降钙素基因相关肽(CGRP)神经的耗尽剂]处理的制剂中，L-NAME不增强三七总皂苷或去甲肾上腺素的血管收缩反应。联合灌流降钙素基因相关肽受体拮抗剂CGRP(8-37)和L-NAME可增加三七总皂苷的收缩反应，但不影响去甲肾上腺素的收缩反应。在甲氧胺产生活动张力的制剂中，L-NAME灌流不影响三七总皂苷引起的血管扩张反应。肠系膜动脉免疫染色显示肠系膜动脉内有nNOS免疫阳性神经纤维，辣椒素处理后的肠系膜动脉内无nNOS免疫阳性神经纤维。这些发现表明，从血管周围辣椒素敏感神经释放的NO，在突触前抑制神经源性NE的释放，从而调节肾上腺素能神经传递。
The effects of nonselective nitric-oxide synthase ( NOS) inhibitors [N-omega-nitro-L-arginine methyl ester (L-NAME) and N-omega-nitro-L-arginine (L-NNA)] and specific neuronal NOS ( nNOS) inhibitor [vinyl-L-N-5-(1-imino-3-butenyl)-L-ornithine (L-VNIO)] on adrenergic nerve-mediated vasoconstriction were studied in rat perfused mesenteric vascular beds without endothelium. Perfusion of L-NAME, L-NNA, or L-VNIO markedly augmented vasoconstrictor responses to periarterial nerve stimulation (PNS; 2-8 Hz) without affecting vasoconstriction induced by exogenously injected norepinephrine (NE). Addition of L-arginine, a precursor for the synthesis of nitric oxide (NO), reversed the augmentation of the PNS response by L-NAME. The PNS (8 Hz)-evoked NE release in the perfusate was increased by L-NAME perfusion. In preparations treated with capsaicin [a depleter of calcitonin gene-related peptide (CGRP)-containing nerves], L-NAME did not augment vasoconstrictor responses to PNS or NE injection. Combined perfusion of CGRP(8-37) (a CGRP receptor antagonist) and L-NAME induced additive augmentation of the vasoconstrictor response to PNS but did not affect the response to NE injection. In preparations with active tone produced by methoxamine and in the presence of guanethidine, L-NAME perfusion did not affect the vasodilator response induced by PNS. Immunostaining of the mesenteric artery showed the presence of nNOS-like immunopositive nerve fibers, which were absent in arteries pretreated with capsaicin. These findings suggest that NO, which is released from perivascular capsaicin-sensitive nerves, presynaptically inhibits neurogenic NE release to modulate adrenergic neurotransmission.