The cardiovascular and renal effects of the potent and highly selective μ opioid agonist [Dmt1]DALDA
The cardiovascular and renal effects of the potent and highly selective μ opioid agonist [Dmt1]DALDA
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DOI：
10.1097/00005344-200412000-00005
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发表时间：
2004-12-01
影响因子：
3
通讯作者：
Schiller, PW
中科院分区：
文献类型：
--
作者：
Gutkowska, J;Mukaddam-Daher, S;Schiller, PW
The cardiovascular and renal effects of a mu opioid agonist, [Dmt(1)]DALDA, were studied in conscious Sprague-Dawley rats. During the first hour postinjection, [Dmt(1)]DALDA (0.025-250 mug/rat, IV) evoked a dose-dependent diuresis. The dose of 2.5 mug increased urine volume from 1.0 +/- 0.2 to 3.4 +/- 0.3 mL/h (P < 0.001, n = 30), urinary excretion of sodium, potassium, and cGMP and induced a mild antihypertensive effect. This dose increased cumulative 4-hour urine volume but significantly inhibited sodium and potassium excretions. The renal and cardiovascular effects were abolished by naloxone (4 mg/kg), but not by naloxonazine (35 mg/kg SC), a selective mu-1 receptor antagonist. Pretreatment with 8 mg/kg naloxone methiodide, an opioid antagonist with limited access to the brain, partially inhibited the renal effects of [Dmt(1)]DALDA. Inhibition of nitric oxide synthases with L-NAME (1 mg/kg) had no effect on the renal and cardiovascular actions of [Dmt(1)]DALDA. Plasma ANP and AVP, measured at 20 and 120 minutes after injection, were not altered by 2.5 and 25 mug [Dmt(1)]DALDA. Therefore, [Dmt(1)]DALDA evokes renal and cardiovascular effects that may primarily be mediated by central naloxonazine-insensitive mu opioid receptors (non-mu-1). These findings indicate that the central mu opioid system is involved in the regulatory mechanism of renal handling of sodium and water.
