Nakamura M, Yoshida H, Makita S, Arakawa N, Niinuma H, Hiramori K
Second Department of Internal Medicine, Iwate Medical University, Japan.
Circulation. 1997 Mar 4;95(5):1214-21. doi: 10.1161/01.cir.95.5.1214.
Adrenomedullin (ADM) is a recently discovered hypotensive peptide that has been isolated from human pheochromocytoma cells. Observations that ADM is produced from cardiovascular tissue and is found in plasma suggest that it may be important in the regulation of regional vascular resistance.
Limb vascular responses to ADM were examined in 10 healthy subjects and compared with those in 18 patients with chronic heart failure (CHF). The peptide increased forearm blood flow (FBF) from 2.7 +/- 0.3 to 11.8 +/- 0.9 mL.min-1.100 mL-1 in the control group and from 2.4 +/- 0.3 to 6.5 +/- 0.7 mL.min-1.100 mL-1 in the CHF group. The ADM-induced FBF increase was significantly impaired in the CHF group (P < .01). After cessation of the infusion, an increased FBF level was sustained for > 60 minutes in the control group, whereas in the CHF group the response returned to the baseline in < 30 minutes. The ADM infusion increased forearm skin blood flow in both groups (P < .05), whereas the skin blood flow response was impaired in the CHF group (P < .01). The role of nitric oxide in ADM-induced vasorelaxation was also studied in 11 healthy subjects and 6 patients with CHF. FBF and skin blood flow responses during ADM administration were significantly attenuated by NG-monomethyl-L-arginine administration in healthy control subjects (P < .05), whereas both flow responses remained the same in the CHF group.
These observations demonstrate that ADM exerts a potent and long-lasting vasodilatory effect on skeletal muscle arteries with involvement of nitric oxide-dependent mechanisms in normal human peripheral vasculature and that these vascular effects are significantly attenuated in patients with CHF, in part because of impaired production of nitric oxide in the forearm resistance vessels.
肾上腺髓质素（ADM）是一种最近从人嗜铬细胞瘤细胞中分离出的降压肽。有观察表明，ADM由心血管组织产生并存在于血浆中，提示其可能在调节局部血管阻力方面发挥重要作用。
对10名健康受试者和18名慢性心力衰竭（CHF）患者的肢体血管对ADM的反应进行了检测，并进行比较。该肽使对照组前臂血流量（FBF）从2.7±0.3增加至11.8±0.9 mL·min⁻¹·100 mL⁻¹，使CHF组从2.4±0.3增加至6.5±0.7 mL·min⁻¹·100 mL⁻¹。CHF组中ADM诱导的FBF增加明显受损（P<0.01）。停止输注后，对照组中升高的FBF水平持续>60分钟，而CHF组的反应在<30分钟内恢复至基线。ADM输注使两组的前臂皮肤血流量均增加（P<0.05），而CHF组的皮肤血流量反应受损（P<0.01）。还在11名健康受试者和6名CHF患者中研究了一氧化氮在ADM诱导的血管舒张中的作用。在健康对照受试者中，给予NG-单甲基-L-精氨酸后，ADM给药期间的FBF和皮肤血流量反应明显减弱（P<0.05），而CHF组的两种血流量反应保持不变。
这些观察结果表明，ADM对骨骼肌动脉具有强大且持久的血管舒张作用，在正常人体外周血管系统中涉及一氧化氮依赖性机制，并且这些血管效应在CHF患者中明显减弱，部分原因是前臂阻力血管中一氧化氮生成受损。
