Diuretic effects of L-threo-3,4-dihydroxyphenylserine(L-threo-DOPS) in anesthetized rats.
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概要
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A synthetic amino acid, L-threo-3, 4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxy!ase (AADC) in various mammalian tissues. Recent studies have indicated the pressor and diuretic effects of L-threo-DOPS. In this study, we examined the effects of L-threo-COPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 μg/kg/min exerted a significant increase in mean arterial pressure (MAP). There was a slight but nonsignificant decrease in renal blood flow (RBF). Although the glomerular filtration rate (GFR) remained at a constant level, urine flow (UF) and Urinary sodium excretion (U<SUB>Na</SUB>V) increased significantly during the drug infusion. Pretreatment with AADC inhibitor, benserazide, completely blocked both the pressor and diuretic effects of L-threo-DOPS. When the renal perfusion pressure was protected from the pressor effect of the drug by using a Blalock clamp, the drug-induced diuresis was abolished. The diuretic effect of L-threo-DOPS was markedly attenuated by the administration of phentolamine. There was a positive correlation between plasma NE concentration and OF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threoDOPS at 20 μg/kg/min was without effect on renal function. These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral α-adrenoceptor activation.
- 公益社団法人 日本薬理学会の論文
著者
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Matsumura Yasuo
Department Of Mechanical Physics Kyoto University
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Morimoto Shiro
Department Of Pharmacology Osaka College Of Pharmacy
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Takahashi Yoshiyuki
Department Of Anesthesiology Dokkyo Medical University
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ICHIHARA Toshio
Department of Earth and Space Science, Faculty of Science, Osaka University
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Ohyama Tadashi
Department of Mining Faculty of Engineering Tohoku University
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ICHIHARA Toshio
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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HISAKI Kazuhiro
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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SHINYAMA Hiroshi
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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OHYAMA Tadashi
Department of Pharmacology, Osaka University of Pharmaceutical Sciences
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Morimoto Shiro
Department of Chemical Engineering, Faculty of Engineering, Tokushima University
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Takahashi Yoshiyuki
Department Of Anesthesia And Pain Medicine, Dokkyo Medical University School Of Medicine
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