Kapusta D R, Dzialowski E M
Department of Pharmacology, LSU Medical Center, New Orleans, LA 70112, USA.
Life Sci. 1995;56(14):PL243-8. doi: 10.1016/0024-3205(95)00065-e.
Central administration of the selective mu opioid agonist, dermorphin, produces a concurrent diuretic and antinatriuretic response in conscious rats. To determine whether central mu opioids differentially affect the renal excretion of water and sodium, we examined changes in renal function produced by intracerebroventricular (i.c.v.) administration of dermorphin during continuous intravenous (i.v.) infusion of a synthetic ADH analogue in conscious Sprague-Dawley rats. During ADH infusion the typical diuresis produced by i.c.v. dermorphin was abolished although the antinatriuresis remained intact. Alone, i.v. ADH produced a decrease in urine flow rate without significantly altering urinary sodium excretion. In other studies, the effects of i.c.v. dermorphin were examined on the renal responses produced by i.v. infusion of a V2-ADH receptor antagonist. In these studies the magnitude of the V2 antagonist-induced diuresis was not altered by i.c.v. dermorphin but the increase in urinary sodium excretion produced by this antagonist was converted to an antinatriuresis. Central dermorphin did not alter heart rate or mean arterial pressure in either study. These findings suggest that the effects of central dermorphin on renal sodium and water handling are mediated by separate mechanisms; the effects on water involving changes in circulating ADH levels and the effects on sodium independent of the action of this hormone.
选择性μ阿片受体激动剂德尔吗啡的中枢给药在清醒大鼠中可同时产生利尿和抗利尿钠反应。为了确定中枢μ阿片类药物是否对水和钠的肾排泄有不同影响，我们在清醒的Sprague-Dawley大鼠连续静脉输注合成抗利尿激素类似物期间，研究了脑室内（i.c.v.）注射德尔吗啡所产生的肾功能变化。在输注抗利尿激素期间，i.c.v. 德尔吗啡产生的典型利尿作用被消除，尽管抗利尿钠作用仍然存在。单独静脉注射抗利尿激素可使尿流率降低，而对尿钠排泄无显著影响。在其他研究中，研究了i.c.v. 德尔吗啡对静脉输注V2抗利尿激素受体拮抗剂所产生的肾脏反应的影响。在这些研究中，i.c.v. 德尔吗啡并未改变V2拮抗剂诱导的利尿幅度，但该拮抗剂所产生的尿钠排泄增加却转变为抗利尿钠作用。在两项研究中，中枢德尔吗啡均未改变心率或平均动脉压。这些发现表明，中枢德尔吗啡对肾脏钠和水处理的影响是由不同机制介导的；对水的影响涉及循环抗利尿激素水平的变化，而对钠的影响则独立于该激素的作用。
