REGIONAL HEMODYNAMIC-EFFECTS OF ENDOTHELIN-1 IN RAT AND MAN - UNEXPECTED ADVERSE REACTIONS
REGIONAL HEMODYNAMIC-EFFECTS OF ENDOTHELIN-1 IN RAT AND MAN - UNEXPECTED ADVERSE REACTIONS
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DOI：
10.1097/00004872-199009000-00004
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发表时间：
1990-09-01
影响因子：
4.9
通讯作者：
HANSSON, L
中科院分区：
文献类型：
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作者：
DAHLOF, B;GUSTAFSSON, D;HANSSON, L
内皮素-1输注于两名男性非优势肱动脉。然后我们监测动脉内平均血压、右房压、心率和前臂血流量（通过体积脉搏图）。内皮素-1的剂量为5。10-14到5倍。10-9 mol，连续5分钟输注，平均动脉压、心率和右房压无明显变化。我们观察到前臂血流量最初增加，随后剂量依赖性减少25%，34%和42%。10-11到5倍。10:9摩尔。高剂量的内皮素1.5倍。如果只给其中一个受试者10-8 mol，就会引起出汗和呕吐。在本例中，平均动脉压、右房压和心率没有变化，而前臂血流量短暂增加。注射内皮素-1后30分钟（最长2小时，持续时间10小时），前臂出现深部肌肉疼痛，这种疼痛通过触摸和肌肉收缩而加剧。前臂肌肉收缩力明显减弱，出现明显水肿。为了探讨水肿形成的机制，内皮素-1(10-10 ~ 5。10-8 mol/l)在大鼠后肢制剂中以恒定流速灌注。在大鼠中，内皮素-1增加了毛细血管前和后的阻力，导致毛细血管静水压力增加，并导致明显的经毛细血管液体从灌注液向组织的净转移。没有血管通透性增加的迹象。这些结果表明，人类水肿的发展可能是由于毛细血管压力的增加。内皮素肽与沙拉毒素毒性的相似性表明，在获得其生理或药理学特性的进一步数据之前，应非常谨慎地在人体中进行测试。
Endothelin-1 was infused into the non-dominant brachial artery in two male subjects. We then monitored intra-arterial mean blood pressure, right atrial pressure, the heart rate and forearm blood flow (by plethysmography). Endothelin-1 at a dose of 5 .times. 10-14 to 5 .times. 10-9 mol, infused over 5 min periods, elicited no major changes in mean arterial pressure, heart rate and right atrial pressure. We observed an initial increase in forearm blood flow, followed by dose-dependent decreases of 25, 34 and 42% at 5 .times. 10-11 to 5 .times. 10-9 mol. A higher dose of endothelin-1, 5 .times. 10-8 mol, given to only one of the subjects, elicited sweating and vomiting. In this subject, mean arterial pressure, right atrial pressure and the heart rate did not change, while forearm blood flow increased transiently. A deep muscular pain developed in the forearm receiving the endothelin-1 infusion after 30 min (maximum 2 h, duration 10 h), and this pain was intensified by touch and muscle contractions. The force of muscle contractions in the forearm was markedly reduced and a visible oedema developed. In order to investigate the mechanisms of oedema formation, endothelin-1 (10-10 to 5 .times. 10-8 mol/l) was given intra-arterially in a rat hindquarter preparation which was perfused at a constant flow rate. In the rat, endothelin-1 increased both pre- and postcapillary resistance, leading to an increase in capillary hyrostatic pressure and a marked net transcapillary fluid transfer from the perfusate to tissue. There was no sign of increased vascular permeability. These results indicate that the development of oedema in humans may be due to an increase in capillary pressure. The similarity to sarafotoxin toxicity suggests that endothelin peptides should be tested in humans with great caution until further data on their physiological or pharmacological properties are available.