Conrad K P, Gellai M, North W G, Valtin H
Department of Physiology, University of New Mexico School of Medicine, Albuquerque 87131.
Ann N Y Acad Sci. 1993 Jul 22;689:346-62. doi: 10.1111/j.1749-6632.1993.tb55559.x.
Acute administration of physiological doses of synthetic OT to conscious Long-Evans and Brattleboro homozygous diabetes insipidus rats produced a modest increase in GFR and effective filtration fraction. Chronic administration of OT to DI rats for 9 days in dosages that were antidiuretic (plasma OT ca. 100 pg/ml) increased both GFR and ERPF by 40%. Table 1 summarizes these renal hemodynamic changes and compares them to the renal effects of VP. Further investigation is needed to define the mechanisms responsible for the changes in GFR and/or ERPF produced by acute and chronic administration of OT to conscious rats. Acute administration of physiological doses of synthetic OT to conscious LE and DI rats also produced a brisk natriuresis with a marked increase in the fractional excretion of sodium. A natriuresis was also observed in conscious Sprague-Dawley rats administered physiological amounts of OT by subcutaneous osmotic minipump. The natriuretic effect of the hormone was short lived, however, being observed only during the first 24-hr period of treatment. The nephron site where OT exerts its natriuretic action, either directly or indirectly, is unknown. Renal prostaglandins may contribute to OT-induced natriuresis, but other mechanisms such as increased renal production of nitric oxide and cGMP have not been tested. Although the natriuretic response to OT has also been described for conscious dogs, it probably does not occur in humans and nonhuman primates. Precise localization of specific renal OT receptors has recently been reported for the rat. OT receptors were identified in the macula densa cells of the adult, rat kidney. This location suggests a possible role for OT in the regulation of tubuloglomerular feedback and solute transport. The signal transduction of the renal OT receptor has been recently evaluated in various kidney epithelial cells in culture. OT stimulates phosphoinositide hydrolysis and increases cytosolic calcium concentrations. In fact, VP produces similar cellular responses in renal epithelia, possibly through the OT receptor. Also, OT stimulates soluble guanylate cyclase and increases intracellular cGMP. Whether OT activates soluble guanylate cyclase secondarily through the production of nitric oxide has not been tested. An important role for OT in renal sodium homeostasis under basal conditions is likely, at least for the rat. Moreover, OT possibly mediates dehydration natriuresis in lower animal species. The contribution of OT to renal physiology in humans and in nonhuman primates, if any, remains uncertain.
给清醒的Long-Evans大鼠和Brattleboro纯合子尿崩症大鼠急性注射生理剂量的合成催产素（OT），可使肾小球滤过率（GFR）和有效滤过分数适度增加。以抗利尿剂量（血浆OT约100 pg/ml）给尿崩症大鼠慢性注射OT 9天，可使GFR和有效肾血浆流量（ERPF）均增加40%。表1总结了这些肾脏血流动力学变化，并将其与血管加压素（VP）的肾脏效应进行了比较。需要进一步研究来确定清醒大鼠急性和慢性注射OT后GFR和/或ERPF变化的机制。给清醒的LE大鼠和DI大鼠急性注射生理剂量的合成OT，还会引起快速利钠，钠分数排泄显著增加。通过皮下渗透微型泵给清醒的Sprague-Dawley大鼠注射生理量的OT也观察到了利钠作用。然而，该激素的利钠作用持续时间较短，仅在治疗的前24小时内观察到。OT直接或间接发挥利钠作用的肾单位部位尚不清楚。肾前列腺素可能参与OT诱导的利钠作用，但其他机制，如肾脏一氧化氮和环磷酸鸟苷（cGMP）生成增加，尚未得到验证。尽管清醒犬也有对OT的利钠反应的描述，但在人类和非人类灵长类动物中可能不会发生。最近报道了大鼠肾脏中特定OT受体的精确定位。在成年大鼠肾脏的致密斑细胞中鉴定出了OT受体。这一位置表明OT在肾小管-肾小球反馈和溶质转运调节中可能发挥作用。最近在培养的各种肾上皮细胞中评估了肾脏OT受体的信号转导。OT刺激磷酸肌醇水解并增加胞质钙浓度。事实上，VP在肾上皮细胞中产生类似的细胞反应，可能是通过OT受体。此外，OT刺激可溶性鸟苷酸环化酶并增加细胞内cGMP。OT是否通过一氧化氮的产生继发激活可溶性鸟苷酸环化酶尚未得到验证。至少对于大鼠来说，OT在基础条件下的肾脏钠稳态中可能发挥重要作用。此外，OT可能介导低等动物物种的脱水利钠作用。OT对人类和非人类灵长类动物肾脏生理学的贡献（如果有的话）仍然不确定。
