Kinter L B, Beeuwkes R
Am J Physiol. 1982 Nov;243(5):R491-9. doi: 10.1152/ajpregu.1982.243.5.R491.
In hypothalamic diabetes insipidus, water balance is achieved primarily through the thirst mechanism. The administration of an antidiuretic agent in the drinking water should restore the antidiuretic response to volume and osmoregulatory drive. To test this hypothesis, homozygous Brattleboro strain rats were given arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (dDAVP) in the drinking water in concentrations of 10-10,000 micrograms/l (AVP) and 5-10,000 micrograms/l (dDAVP). Oral AVP was found to be ineffective. Oral dDAVP resulted in 1) a progressive increase in dDAVP dose, from 2.3 to 2,559 micrograms.day-1.kg-1; 2) a dose-dependent increase in urine osmolality from 306 to 1,796 mosmol/kg; and 3) a dose-dependent decrease in urinary solute excretion. At each dDAVP dose level, stable physiological states were achieved within 24 h. Similar antidiuretic states were achieved when dDAVP was administered in increasing doses or when therapy was initiated at a high dose. These findings demonstrate that inclusion of an appropriate antidiuretic agent in the drinking water can restore the renal response to volume-osmoregulatory drive.
在下丘脑性尿崩症中，水平衡主要通过口渴机制来实现。在饮用水中给予抗利尿药物应能恢复对容量和渗透压调节驱动的抗利尿反应。为验证这一假设，给纯合布拉特洛维大鼠饮用含精氨酸加压素（AVP）或1-去氨基-8-D-精氨酸加压素（dDAVP）的水，浓度分别为10 - 10,000微克/升（AVP）和5 - 10,000微克/升（dDAVP）。发现口服AVP无效。口服dDAVP导致：1）dDAVP剂量逐渐增加，从2.3微克·天⁻¹·千克⁻¹增至2,559微克·天⁻¹·千克⁻¹；2）尿渗透压呈剂量依赖性增加，从306毫摩尔/千克增至1,796毫摩尔/千克；3）尿溶质排泄呈剂量依赖性减少。在每个dDAVP剂量水平，24小时内可达到稳定的生理状态。当以递增剂量给予dDAVP或从高剂量开始治疗时，可达到类似的抗利尿状态。这些发现表明，在饮用水中加入适当的抗利尿药物可恢复肾脏对容量 - 渗透压调节驱动的反应。
