Hohage H, Schlatter E, Greven J
Medizinische Poliklinik, Westfälischen Wilhelms-Universität Münster, Germany.
Clin Nephrol. 1997 May;47(5):316-24.
Using classical clearance techniques, the renal effects of moxonidine and clonidine were studied in the rat. Moxonidine (0.25 and 0.5 mg/kg body weight i.v.) increased transiently fractional fluid and Na+ excretion. Similarly, clonidine in the same i.v. doses caused a sustained increase in fractional fluid excretion, but only a short lasting increase in fractional Na+ excretion that was similar to the effect of moxonidine. Water diuresis experiments showed that the agonists mostly exert their actions within the proximal tubule. Antagonists such as idazoxan and yohimbine did not change fractional fluid excretion and Na+ excretion by their own. Both, the nonselective imidazoline/alpha 2-adrenoceptor antagonist idazoxan and the pure alpha 2-adrenoceptor antagonist yohimbine attenuated the moxonidine induced effects on fractional fluid excretion and Na+ excretion. The clonidine induced increase in fractional fluid and Na(+)-excretion was inhibited by yohimbine and desmopressin only. The effects on systemic blood pressure after moxonidine or clonidine application were similar. The initial blood pressure increases after moxonidine application, however, was less than with clonidine, whereas the hypotensive potency was more pronounced. Similar to the effects on kidney function, idazoxan and yohimbine had no influence on systemic blood pressure by themselves. Immediately after moxonidine application, a short lasting increase in renal plasma flow and glomerular filtration rate could be observed. Our results demonstrate, that moxonidine exerts renal effects, which are different from those of clonidine. At present time, renal effects mediated by imidazoline receptors and alpha 2-adrenoceptors cannot be clearly distinguished.
采用经典的清除技术,在大鼠中研究了莫索尼定和可乐定对肾脏的影响。莫索尼定(静脉注射0.25和0.5mg/kg体重)可使尿钠排泄分数和液体排泄分数短暂增加。同样,相同静脉注射剂量的可乐定可使液体排泄分数持续增加,但尿钠排泄分数仅短暂增加,且与莫索尼定的作用相似。水利尿实验表明,这些激动剂主要在近端小管发挥作用。伊达唑啉和育亨宾等拮抗剂自身不会改变液体排泄分数和尿钠排泄分数。非选择性咪唑啉/α2肾上腺素能受体拮抗剂伊达唑啉和纯α2肾上腺素能受体拮抗剂育亨宾均可减弱莫索尼定对液体排泄分数和尿钠排泄分数的诱导作用。可乐定诱导的液体排泄分数和尿钠排泄增加仅被育亨宾和去氨加压素抑制。应用莫索尼定或可乐定后对全身血压的影响相似。然而,应用莫索尼定后最初的血压升高幅度小于可乐定,而其降压效力更为显著。与对肾功能的影响相似,伊达唑啉和育亨宾自身对全身血压无影响。应用莫索尼定后即刻,可观察到肾血浆流量和肾小球滤过率短暂增加。我们的结果表明,莫索尼定的肾脏作用与可乐定不同。目前,尚无法明确区分由咪唑啉受体和α2肾上腺素能受体介导的肾脏作用。