Troughton R W, Frampton C M, Lewis L K, Yandle T G, Richards A M, Nicholls M G
The Christchurch Cardioendocrine Research Group, Christchurch Hospital and School of Medicine, Riccarton Avenue, Christchurch, New Zealand.
Clin Sci (Lond). 2001 Jul;101(1):103-9.
Experimental data indicate that adrenomedullin (AM) interacts at various levels with the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis, but data from humans are scant. We examined the effects of intermediate-dose, short-term AM infusion on angiotensin II- and adrenocorticotrophic hormone (ACTH)-mediated hormone and haemodynamic responses in healthy subjects. Seven normal volunteers (age 18-25 years) completed a placebo-controlled crossover study. Each subject was studied on day 4 of two periods of a low-salt diet (40 mmol of sodium and 80 mmol of potassium daily), receiving incremental infusions of angiotensin II in the morning and ACTH in the afternoon of each study day, on a background infusion of AM (4 pmol.min(-1).kg(-1)) or vehicle (hemaccel). Achieved plasma AM levels (23+/-6 pmol/l) and peak angiotensin II levels (160 pmol/l) were similar on the two experimental days. While the pressor action of angiotensin II was attenuated by AM (P<0.01) and noradrenaline levels rose (P<0.05), the aldosterone response was unaltered. During ACTH infusion, AM increased heart rate (P<0.01), plasma adrenaline (P<0.01) and plasma noradrenaline (P<0.05), and augmented the cortisol response (P<0.01), but was without effect on aldosterone levels and blood pressure. We conclude that the threshold for the effects of AM on aldosterone secretion in humans is set higher than for other biological responses to this hormone, namely blood pressure, heart rate, sympathetic activity and cortisol secretion, under these experimental conditions.
实验数据表明，肾上腺髓质素（AM）在多个水平上与肾素 - 血管紧张素 - 醛固酮系统以及下丘脑 - 垂体 - 肾上腺轴相互作用，但来自人类的数据却很少。我们研究了中等剂量、短期输注AM对健康受试者中血管紧张素II和促肾上腺皮质激素（ACTH）介导的激素及血流动力学反应的影响。七名正常志愿者（年龄18 - 25岁）完成了一项安慰剂对照交叉研究。在两个低盐饮食期（每日40 mmol钠和80 mmol钾）的第4天对每位受试者进行研究，在每个研究日的上午递增输注血管紧张素II，下午递增输注ACTH，同时背景输注AM（4 pmol·min⁻¹·kg⁻¹）或赋形剂（贺斯）。在两个实验日，达到的血浆AM水平（23±6 pmol/l）和峰值血管紧张素II水平（160 pmol/l）相似。虽然AM减弱了血管紧张素II的升压作用（P<0.01）且去甲肾上腺素水平升高（P<0.05），但醛固酮反应未改变。在输注ACTH期间，AM增加了心率（P<0.01）、血浆肾上腺素（P<0.01）和血浆去甲肾上腺素（P<0.05），并增强了皮质醇反应（P<0.01），但对醛固酮水平和血压无影响。我们得出结论，在这些实验条件下，人类中AM对醛固酮分泌的作用阈值设定得高于对该激素的其他生物学反应，即血压、心率、交感神经活动和皮质醇分泌。
