Role of nitric oxide in mediating vasodilator responses to opioid peptides in the rat
Role of nitric oxide in mediating vasodilator responses to opioid peptides in the rat
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DOI：
10.1046/j.1440-1681.2002.03634.x
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发表时间：
2002-03-01
影响因子：
2.9
通讯作者：
Kadowitz, PJ
中科院分区：
文献类型：
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作者：
Champion, HC;Bivalacqua, TJ;Kadowitz, PJ
1.内吗啡肽1和2，μ-阿片受体的内源性配体，以及痛敏肽（nociceptin，OFQ），ORL 1受体的内源性配体，在大鼠后躯的血管床中具有血管扩张活性。本研究探讨了一氧化氮（NO）、扩血管活性素和K-ATP通道开放在介导这些新型激动剂扩血管反应中的作用.在恒流条件下，注射内吗啡肽1和2、PL 017（[N-MePhe（3），D-Pro（4）]-morphiceptin）、痛敏肽和Tyr-D-Ala-Gly-MePhe-Gly（ol）-脑啡肽（DAMGO）引起后躯灌注压的剂量依赖性降低。NO合成酶抑制剂N-G-nitro-L-arginine methyl ester（L-NAME）可减弱内吗啡肽1和2、乙酰胆碱和肾上腺髓质素对血管的舒张作用，而对痛敏肽、肾上腺髓质素和NO供体二乙胺/NO的舒张作用无明显改变.当对花生四烯酸的血管舒张反应显著降低时，给予甲氨蝶呤钠后，或当对左克罗卡林的血管舒张反应显著降低时，给予U-37883 A后，对内吗啡肽1和2、痛敏肽、PL 017和DAMGO的血管舒张反应没有改变.这些研究的结果表明，内吗啡肽1和2，PL 017和DAMGO的血管扩张反应介导的，在很大程度上，通过释放NO，而血管扩张反应痛敏肽介导的L-NAME不敏感的机制。此外，这些结果表明，这些肽的血管扩张反应不是由于释放血管扩张素或开放的K-ATP通道在后躯血管床的大鼠。
1. Endomorphins 1 and 2, endogenous ligands for the mu-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of K-ATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat.2. Under constant-flow conditions, injections of endomorphins 1 and 2, PL017 ([N-MePhe(3) ,D-Pro(4)]-morphiceptin), nociceptin and Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) at a time when vasodilator responses to nociceptin, adrenomedullin and the NO donor diethylamine/NO were not altered.3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly.4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that the vasodilator responses to these peptides are not due to the release of vasodilator prostaglandins or the opening of K-ATP channels in the hindquarters vascular bed of the rat.