Barthelmebs M, Vailly B, Velly J, Ehrhardt J D, Grima M, Imbs J L
Institut de Pharmacologie, URA D0589 CNRS, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Am J Hypertens. 1990 Jun;3(6 Pt 2):18S-21S. doi: 10.1093/ajh/3.6.18s.
In the Wistar rat in vivo L-dopa (10 mg/kg, subcutaneously) was shown to have the characteristics of a kidney-directed dopamine (DA) prodrug: two daily injections increased 24 h urinary DA excretion 450-fold but had no systemic effects on blood pressure and heart rate. In inactin-anesthesized rats, L-dopa increased natriuresis, diuresis and renal blood flow; these effects were linked to endorenal DA synthesis and to DA-1 receptor stimulation since they were suppressed by both carbidopa and SCH 23390. In the isolated perfused rat kidney, DA was synthesized from L-dopa with a greater yield than from gludopa. In nonfiltering kidneys, L-dopa metabolism was not limited when the access to dopa decarboxylase was restricted to the basolateral membrane. The same was not true for gludopa, for which the basolateral metabolism was low.
在Wistar大鼠体内,左旋多巴(10毫克/千克,皮下注射)显示出具有肾脏导向多巴胺(DA)前体药物的特性:每日两次注射使24小时尿多巴胺排泄增加450倍,但对血压和心率无全身影响。在硫喷妥钠麻醉的大鼠中,左旋多巴增加了利钠、利尿和肾血流量;这些作用与肾内多巴胺合成和多巴胺-1受体刺激有关,因为它们被卡比多巴和SCH 23390所抑制。在离体灌注的大鼠肾脏中,左旋多巴合成多巴胺的产量高于谷氨酸脱羧酶。在非滤过性肾脏中,当多巴脱羧酶的作用仅限于基底外侧膜时,左旋多巴的代谢不受限制。而谷氨酸脱羧酶并非如此,其基底外侧代谢较低。