ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE REGULATION OF BLOOD-PRESSURE
ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE REGULATION OF BLOOD-PRESSURE
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DOI：
10.1073/pnas.86.9.3375
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
MONCADA, S
中科院分区：
文献类型：
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作者：
REES, DD;PALMER, RMJ;MONCADA, S
使用NΩ-单甲基-L-精氨酸（L-NMMA）（一种从L-精氨酸形成一氧化氮的特异性抑制剂）研究了内皮源性一氧化氮在麻醉兔血压调节中的作用。 L-NMMA (3-100 mg.cntdot.kg-1)，而非其 D-对映体，可诱导平均全身动脉血压出现剂量依赖性持久（15-90 分钟）升高。 L-NMMA (100 mg.cntdot.kg-1) 也显着抑制乙酰胆碱的降血压作用，而不影响三硝酸甘油酯的降血压作用。 L-NMMA 的这两种作用均可被 L-精氨酸 (300 mg.cntdot.kg-1) 逆转，但不能被 D-精氨酸 (300 mg.cntdot.kg-1)、吲哚美辛 (1 mg.cntdot.kg-1)、哌唑嗪 (0.3 mg.cntdot.kg-1) 或迷走神经切断术逆转。 L-NMMA 的体内作用与离体灌注主动脉段释放一氧化氮的显着抑制有关。通过主动脉段注入L-精氨酸可以逆转这种抑制作用。这些结果表明血管内皮从L-精氨酸形成一氧化氮在血压调节和乙酰胆碱的降血压作用中发挥作用。
The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N.omega.-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.cntdot.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.cntdot.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.cntdot.kg-1), but not by D-arginine (300 mg.cntdot.kg-1), indomethacin (1 mg.cntdot.kg-1), prazosin (0.3 mg.cntdot.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.