INHIBITION OF DOPAMINE β-HYDROXYLASE IN BLOOD VESSELS BY PICOLINIC ACID DERIVATIVES <I>IN VIVO</I> AND THEIR ANTIHYPERTENSIVE EFFECTS
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概要
- 論文の詳細を見る
The effect of picolinic acid derivatives, 5-butylpicolinic (fusaric) acid (FA), 5-(3, 4-dibromobutyl)picolinic acid(Br<SUB>2</SUB>FA)and 5-(N-N-dimethyldithiocarbamoilmethyl) picolinic acid (YP-279) on dopamine β-hydroxylase in blood vessels <I>in vivo</I> was studied. Maximum inhibition of the conversion of <SUP>14</SUP>C-dopamine (<SUP>14</SUP>C-DA) to <SUP>14</SUP>C-norepinephrine <SUP>14</SUP>C-NE) in rat aorta, mesenteric artery and renal artery was detected 30 min after FA and Br<SUB>2</SUB>FA (75 mg/kg) and 60 min after YP-279 (75 mg/kg). NE synthesis from <SUP>14</SUP>C-DA returned to near control values by 6 hr in the blood vessels. NE levels of the aorta and mesenteric artery were significantly reduced by 30 to 50 % at 4 hr after Br<SUB>2</SUB>FA or FA (75 mg/kg). Dopamine β-hydroxylase (DBH) activity, using tyramine as substrate, in heart, aorta, mesenteric artery and renal artery was markedly reduced. The concentrations of FA, Br<SUB>2</SUB>FA and YP-279 in rat blood following a single i.p. injection of each drug increase rapidly, reaching highest values in 0 to 30 min and decreasing slowly to 0 after 6 hr. These compounds did not affect the uptake of <SUP>3</SUP>H-NE into the rat heart. These three compounds were found to lower blood pressure effectively in normal Wistar rats (above 25 mg/kg).
- 社団法人 日本薬理学会の論文
著者
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Hashizume Yoshio
Department Of Neuropathology Institute For Medical Science Of Aging Aichi Medical University
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Hidaka Hiroyoshi
Department Of Pharmacology Nagoya University School Of Medicine
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Yamamoto Masahiro
Department Of Earth Sciences Okayama University
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SHOKA Fumiko
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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TAKEMOTO Nobutaka
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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Hidaka Hiroyoshi
Department Of Pharmacology Mie University
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Yamamoto Masahiro
Department Of Agricultural Chemistry Faculty Of Agriculture Niigata University
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HIDAKA Hiroyoshi
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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YAMAMOTO Masahiro
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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HASHIZUME Yoshio
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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