Christensen S, Geisler A
Acta Pharmacol Toxicol (Copenh). 1977 Mar;40(3):447-54.
The antidiuretic and urinary cyclic AMP response to supramaximal vasopressin infusion was studied in normal rats and in rats with lithium-polyuria. The animals were anaesthetized and then infused with a solution designed to produce excessive water diuresis and to lower basal cyclic AMP excretion. In 6 control animals not infused with vasopressin (1) urinary cyclic AMP excretion decreased during the infusion period. Vasopressin infusion (300 muU/min.) consistantly induced antidiuresis in all of 13 control rats (II); but the urinary cyclic AMP response varied individually from a significant increase in 6 animals to either no change or to a decrease in the remaining animals. The antidiuretic response to vasopressin was inhibited by 85% in 10 animals with marked polyuria induced by lithium administration (III). None of the animals in this group showed a significant increase of cyclic AMP excretion in response to vasopressin. The average rate of cyclic AMP excretion, which was equal in the two groups before vasopressin, was signifimantly lower in group III than in group II during vasopressin infusion. It is suggested that the increase in cyclic AMP excretion during vasopressin antidiuresis, although not consistant, most likely reflects hormone-induced changes of intracellular cyclic AMP levels in the renal medulla. Thus, the data suggest that the nephrogenic diabetes insipidus syndrome produced by lithium is associated with a defect in the renal formation of cyclic AMP in response to vasopressin.
在正常大鼠和锂诱导多尿的大鼠中，研究了抗利尿和尿中环磷酸腺苷（cAMP）对超大剂量血管加压素输注的反应。将动物麻醉，然后输注一种溶液，该溶液旨在产生过多的水利尿并降低基础cAMP排泄。在6只未输注血管加压素的对照动物中，（1）在输注期间尿cAMP排泄减少。血管加压素输注（300mU/min）在所有13只对照大鼠中均持续诱导抗利尿作用（II）；但尿cAMP反应个体差异较大，6只动物显著增加，其余动物无变化或减少。在10只因锂给药而出现明显多尿的动物中，血管加压素的抗利尿反应被抑制了85%（III）。该组动物中没有一只对血管加压素产生cAMP排泄的显著增加。在输注血管加压素之前，两组的cAMP排泄平均速率相等，但在输注血管加压素期间，III组明显低于II组。提示血管加压素抗利尿期间cAMP排泄的增加虽然不恒定，但很可能反映了激素诱导的肾髓质细胞内cAMP水平的变化。因此，数据表明锂诱导的肾性尿崩症综合征与肾对血管加压素反应时cAMP生成缺陷有关。
