Walker L A, Murphy J C
J Pharmacol Exp Ther. 1984 May;229(2):404-8.
The renal response to the acute administration of morphine was examined in conscious, chronically catheterized, nonhydrated rats. After control clearance periods, morphine sulfate was injected i.v. at 4 mg/kg followed by an infusion of 2 mg/kg X hr. Morphine caused an increase in urine flow which was variable in magnitude and duration. The initial diuresis was not maintained despite continued morphine administration and replacement of lost fluid. Compared to vehicle treatment morphine also induced marked sodium and chloride retention which was sustained throughout the 2-hr infusion period. There were no changes in blood pressure or heart during the clearance periods, although an initial transient hypotension and bradycardia were observed with morphine injection. There were no changes in glomerular filtration rate which could account for the antinatriuresis. Naloxone pretreatment blocked all of the observed renal responses. The results indicate that morphine exerts its effects on electrolyte excretion by enhancing renal tubular sodium or chloride reabsorption rather than changes in systemic hemodynamics or glomerular filtration rate. In a separate series of experiments, urine osmolality, osmolar clearance and free water clearance were estimated. All rats receiving morphine transiently excreted a hypotonic urine (minimum 183 +/- 23 mOsmol/kg of H2O) with a reduction in osmolar clearance and a sharp increase in free water clearance. These findings are consistent with a temporary inhibition of vasopressin release by morphine.
在清醒、长期插管、未补水的大鼠中研究了吗啡急性给药后的肾脏反应。在对照清除期后，静脉注射4mg/kg硫酸吗啡，随后以2mg/kg·小时的速度输注。吗啡导致尿量增加，其幅度和持续时间各不相同。尽管持续给予吗啡并补充流失的液体，但最初的利尿作用并未持续。与溶剂处理相比，吗啡还诱导了明显的钠和氯潴留，在整个2小时输注期间持续存在。清除期血压和心率无变化，尽管注射吗啡时观察到最初的短暂低血压和心动过缓。肾小球滤过率没有变化，这可以解释钠排泄减少的原因。纳洛酮预处理阻断了所有观察到的肾脏反应。结果表明，吗啡通过增强肾小管钠或氯的重吸收而不是通过全身血流动力学或肾小球滤过率的变化来发挥其对电解质排泄的作用。在另一系列实验中，估计了尿渗透压、渗透清除率和自由水清除率。所有接受吗啡的大鼠均短暂排出低渗尿（最低183±23mOsmol/kg H2O），渗透清除率降低，自由水清除率急剧增加。这些发现与吗啡暂时抑制血管加压素释放一致。
