Dejgaard A, Andersen P, Hvidberg A, Hilsted J
Hvidoere Hospital, Klampenborg, Denmark.
Diabet Med. 1996 Nov;13(11):983-9. doi: 10.1002/(SICI)1096-9136(199611)13:11<983::AID-DIA271>3.0.CO;2-7.
Denervation hypersensitivity is a well-known phenomenon in patients with autonomic failure. In diabetic autonomic neuropathy hypersensitivity to beta-adrenergic stimulation has been demonstrated. We infused noradrenaline, mainly an alpha-adrenoceptor agonist, in three escalating doses (0.5, 2.5, and 5 micrograms min-1) in three age and sex matched groups of eight subjects: healthy volunteers, diabetic patients with and without autonomic neuropathy. During steady state in each infusion period we measured heart rate, blood pressure, cardiac output, hepato-splanchnic blood flow, vascular resistance, glucose kinetics, metabolites (beta-hydroxybuturate, glycerol, and lactate), and glucoregulatory hormones (noradrenaline, adrenaline, growth hormone, pancreatic polypeptide, cortisol, and insulin). Systolic and mean blood pressure increased in all groups but diabetic patients with autonomic neuropathy showed a significantly higher increase (p < 0.01) than the other two groups, with a lower threshold for increase in blood pressure. Cardiac output, hepato-splanchnic blood flow, vascular resistance, and heart rate did not change in any of the groups. The incremental increase in glucose and beta-hydroxybuturate was higher in patients with autonomic neuropathy. Otherwise, only minor changes were seen in hormonal and metabolic parameters. The cardiovascular hypersensitivity seen in diabetic autonomic neuropathy was mainly explained by increased peripheral vascular resistance, which increased significantly (p < 0.05) more in these patients. In conclusion, diabetic patients with autonomic neuropathy show denervation hypersensitivity to alpha-adrenergic stimulation by noradrenaline, especially as regards cardiovascular effects.
去神经超敏反应是自主神经功能衰竭患者中一种众所周知的现象。在糖尿病性自主神经病变中，已证实存在对β-肾上腺素能刺激的超敏反应。我们对三组年龄和性别匹配的每组8名受试者（健康志愿者、有和无自主神经病变的糖尿病患者）以三种递增剂量（0.5、2.5和5微克/分钟）输注主要为α-肾上腺素能受体激动剂的去甲肾上腺素。在每个输注期的稳定状态下，我们测量了心率、血压、心输出量、肝内脏血流量、血管阻力、葡萄糖动力学、代谢产物（β-羟基丁酸盐、甘油和乳酸）以及葡萄糖调节激素（去甲肾上腺素、肾上腺素、生长激素、胰多肽、皮质醇和胰岛素）。所有组的收缩压和平均血压均升高，但有自主神经病变的糖尿病患者的血压升高明显高于其他两组（p < 0.01），且血压升高的阈值较低。所有组的心输出量、肝内脏血流量、血管阻力和心率均无变化。自主神经病变患者的葡萄糖和β-羟基丁酸盐的增量升高更高。否则，在激素和代谢参数方面仅观察到微小变化。糖尿病性自主神经病变中所见的心血管超敏反应主要是由于外周血管阻力增加所致，在这些患者中这种增加更为显著（p < 0.05）。总之，有自主神经病变的糖尿病患者对去甲肾上腺素的α-肾上腺素能刺激表现出去神经超敏反应，尤其是在心血管效应方面。
