Ishikawa S, Schrier R W
J Clin Invest. 1982 Mar;69(3):666-72. doi: 10.1172/jci110494.
Recent reports have suggested that opioid peptides may be involved in renal water excretion. The present in vivo experiments, therefore, were undertaken to determine the effect of opioid peptides on the osmotic and nonosmotic release of arginine vasopressin (AVP) in the conscious rat. Experimental animals were infused intravenously with naloxone (20 mug/kg per min) or oxilorphan (40 mug/kg per min), chemically dissimilar opioid antagonists. Control rats were infused with normal saline, the vehicle for the opioid antagonists. In all three groups the osmotic release of AVP was examined during an acute hypertonic saline (3%) infusion (2 ml/100 g body wt). The antidiuresis following the hypertonic saline infusion was significantly attenuated in naloxone- and oxilorphan-treated rats, as the peak urinary osmolality (Uosm) rose to 581.4+/-22.4 and 558.2+/-27.6 mosmol/kg H(2)O in naloxone- and oxilorphan-treated rats as compared with the value in control rats of 735.3+/-24.2 mosmol/kg H(2)O (both P < 0.001 vs. control). At the same time the plasma AVP levels of 5.4+/-1.3 and 5.2+/-1.1 pg/ml in naloxone- and oxilorphan-treated rats, respectively, were significantly lower than the plasma AVP in control rats of 16.9+/-2.5 pg/ml (P < 0.001). In another three groups of rats the nonosmotic release of AVP was examined during hypovolemia induced by intraperitoneal 6% dextran (1.8 ml/100 g body wt). Following intraperitoneal administration of dextran the peak Uosm of 703.0+/-87.8 and 734.8+/-99.1 mosmol/kg H(2)O in naloxone- and oxilorphan-treated rats, respectively, was significantly less than the value in control rats of 1,169.3+/-135.5 mosmol/kg H(2)O (both P < 0.02 vs. control). A comparable decrease in blood volume of 13% occurred in all three groups of animals. During the dextran administration plasma AVP levels in naloxone- and oxilorphan-treated rats increased to 4.3+/-1.0 and 6.0+/-2.0 pg/ml, respectively; both of these values were significantly lower than the plasma AVP of 12.9+/-1.4 pg/ml in control rats (P < 0.02). The effect of opioid antagonists to impair the osmotic and nonosmotic release of AVP occurred in the absence of differences in mean arterial pressure, glomerular filtration rate and the renal response to AVP. These results, therefore, indicate that opioid peptides are involved in renal water excretion primarily by modulating the central release of AVP.
最近的报告表明，阿片肽可能参与肾脏水排泄过程。因此，进行了本体内实验，以确定阿片肽对清醒大鼠精氨酸加压素（AVP）的渗透和非渗透释放的影响。给实验动物静脉注射纳洛酮（20微克/千克每分钟）或奥昔吗啡（40微克/千克每分钟），这两种化学性质不同的阿片拮抗剂。对照大鼠注射生理盐水，即阿片拮抗剂的溶剂。在所有三组中，在急性输注高渗盐水（3%）（2毫升/100克体重）期间检测AVP的渗透释放。在纳洛酮和奥昔吗啡处理的大鼠中，高渗盐水输注后的抗利尿作用明显减弱，与对照大鼠735.3±24.2毫摩尔/千克H₂O的值相比，纳洛酮和奥昔吗啡处理的大鼠的尿渗透压峰值（Uosm）分别升至581.4±22.4和558.2±27.6毫摩尔/千克H₂O（两者与对照相比P<0.001）。同时，纳洛酮和奥昔吗啡处理的大鼠的血浆AVP水平分别为5.4±1.3和5.2±1.1皮克/毫升，明显低于对照大鼠的血浆AVP水平16.9±2.5皮克/毫升（P<0.001）。在另外三组大鼠中，在腹腔注射6%右旋糖酐（1.8毫升/100克体重）诱导的血容量不足期间检测AVP的非渗透释放。腹腔注射右旋糖酐后，纳洛酮和奥昔吗啡处理的大鼠的峰值Uosm分别为703.0±87.8和734.8±99.1毫摩尔/千克H₂O，明显低于对照大鼠的1169.3±135.5毫摩尔/千克H₂O的值（两者与对照相比P<0.02）。三组动物的血容量均出现了13%的类似下降。在注射右旋糖酐期间，纳洛酮和奥昔吗啡处理的大鼠的血浆AVP水平分别升至4.3±1.0和6.0±2.0皮克/毫升；这两个值均明显低于对照大鼠血浆AVP的12.9±1.4皮克/毫升（P<0.02）。阿片拮抗剂损害AVP的渗透和非渗透释放的作用，是在平均动脉压、肾小球滤过率以及肾脏对AVP的反应无差异的情况下发生的。因此，这些结果表明，阿片肽主要通过调节AVP的中枢释放来参与肾脏水排泄。
