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The renal vascular effects of aporphines and related compounds were studied on the isolated perfused rat kidney in the presence of 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) -3 X 10(-6) M). Under these conditions, (R)-(-)-apomorphine showed renal dopaminomimetic activity, i.e. renal vasodilation competitively inhibited by (+)-butaclamol (10(-8) M) but not by (-)-butaclamol (3 X 10(-8) M). It had an apparent affinity 25 times higher but a markedly lower intrinsic activity than dopamine. N-n-Propyl and trihydroxylated aporphines were less potent and the mono-10-hydroxylated aporphine was completely inactive. (S)-(+)-Bulbocapnine also showed weak dopaminomimetic activity but tetrahydropapaveroline was devoid of such an effect. (-)-N-(2-Chloroethyl)-norapomorphine (10(-5) M) irreversibly antagonised dopamine-induced renal vasodilation. At concentrations above 3 X 10(-6) M, most aporphines and tetrahydropapaveroline induced additional non-dopamine receptor related renal vasodilation.

The renal vascular effects of dopaminomimetics were studied in the isolated perfused rat kidney after pretreatment with 10(-5) M phenoxybenzamine and 10(-5) M sotalol and after contraction of the vascular bed with prostaglandin F2 alpha (10(-7) to 3 x 10(-6) M). Under these conditions, our criterion for vascular dopaminomimetic activity was renal vasodilation, competitively inhibited by d-butaclamol (10(-8) M) but not by 1-butaclamol (3 x 10(-8) M). Dopamine is active at micromolar concentrations (ED50 = 2.53 +/- 0.34 x 10(-6) M). The N-alkylated analogues of dopamine preserve this activity if the alkyl group is a methyl group (epinine) or two n-propyl groups (di-n-propyl-dopamine). The catechol nucleus appears essential for renal vascular dopaminomimetic activity (SK&F 38393, active; p-tyramine, di-n-propyl-m-tyramine and RU 24926, inactive). Bromocriptine reproduces renal dopaminergic vasodilation with an ED50 of 1.3 +/- 0.14 x 10(-6) M. The study of structure-activity relationships of dopaminomimetics relates the vascular dopamine receptor, associated with renal vasodilation, to the dopamine receptor, associated with stimulation of dopamine-sensitive adenylate cyclase.