Hader O, Bähr V, Hensen J, Hofbauer K G, Oelkers W K
Department of Internal Medicine, Klinikum Steglitz, Freie Universität Berlin.
Acta Endocrinol (Copenh). 1990 Dec;123(6):622-8. doi: 10.1530/acta.0.1230622.
Experimental evidence indicates that arginine vasopressin contributes to the release of adrenocorticotropic hormone under certain conditions. We studied for the first time the AVP antagonist [d(CH2)5 Tyr(Me)AVP] in 6 normal men in order to evaluate the possible role of AVP as an ACTH-releasing hormone during insulin-induced hypoglycemia. To test the agent's capacity to inhibit an ACTH release by exogenous AVP, we compared the ACTH response to an infusion of 300 ng AVP/min a. 30 min after injection of 5 micrograms/kg of the antagonist, b. after injection of placebo (0.9% NaCl). Plasma ACTH levels during AVP infusion rose from 17.2 +/- 1.6 ng/l (3.8 +/- 0.35 pmol/l) to 31.7 +/- 4.2 ng/l (7.0 +/- 0.92 pmol/l) at 40 min after injection of the antagonist, the difference to the control-group (increment from 16.5 +/- 1.2 ng/l (3.6 +/- 0.26 pmol/l) to 41.8 +/- 3.5 ng/l) (9.2 +/- 0.77 pmol/l) being significant (p less than 0.05). Peak plasma cortisol levels were 323 +/- 42 and 529 +/- 52 nmol/l, respectively (p less than 0.05). We then tested the compound in the same subjects during an insulin-induced hypoglycemia; 30 min after administration of 10 micrograms/kg of the AVP antagonist or placebo, all subjects received 0.12 IU/kg of normal insulin, thus inducing a fall of blood glucose levels below 2 mmol/l. The AVP antagonist caused a moderate but insignificant reduction of the rise in plasma ACTH and a slightly greater, significant reduction of the increment in plasma cortisol (350 +/- 19 nmol/l with antagonist and 469 +/- 90 nmol/l with placebo, p less than 0.05) during insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
实验证据表明，在某些情况下精氨酸加压素有助于促肾上腺皮质激素的释放。我们首次在6名正常男性中研究了精氨酸加压素拮抗剂[d(CH2)5 Tyr(Me)AVP]，以评估精氨酸加压素在胰岛素诱导的低血糖期间作为促肾上腺皮质激素释放激素的可能作用。为了测试该药物抑制外源性精氨酸加压素释放促肾上腺皮质激素的能力，我们比较了在以下两种情况下促肾上腺皮质激素对以300 ng精氨酸加压素/分钟的速度输注的反应：a. 注射5微克/千克拮抗剂30分钟后；b. 注射安慰剂（0.9%氯化钠）后。在注射拮抗剂后40分钟，输注精氨酸加压素期间血浆促肾上腺皮质激素水平从17.2±1.6 ng/l（3.8±0.35 pmol/l）升至31.7±4.2 ng/l（7.0±0.92 pmol/l），与对照组（从16.5±1.2 ng/l（3.6±0.26 pmol/l）增至41.8±3.5 ng/l）（9.2±0.77 pmol/l）相比差异显著（p<0.05）。血浆皮质醇峰值水平分别为323±42和529±52 nmol/l（p<0.05）。然后我们在同一受试者胰岛素诱导的低血糖期间测试了该化合物；在给予10微克/千克精氨酸加压素拮抗剂或安慰剂30分钟后，所有受试者接受0.12 IU/千克正规胰岛素，从而使血糖水平降至2 mmol/l以下。在胰岛素诱导的低血糖期间，精氨酸加压素拮抗剂使血浆促肾上腺皮质激素升高幅度适度但不显著降低，使血浆皮质醇升高幅度略有更大、显著降低（拮抗剂组为350±19 nmol/l，安慰剂组为469±90 nmol/l，p<0.05）。（摘要截短于250字）
