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Renal Vascular Activity of SK&F 38393 and Dopamine in Anesthetized Dogs

1980; Lippincott Williams & Wilkins; Volume: 2; Issue: 5 Linguagem: Inglês

10.1097/00005344-198009000-00008

1533-4023

R Hahn, Joe R. Wardell,

Blood Pressure and Hypertension Studies

The renal vasodilator activity of SK&F 38393 and dopamine have been compared in anesthetized dogs surgically prepared with arterial blood pressure catheters and renal artery blood flowprobes. Intravenous infusion of SK&F 38393 (10–2,430 μg/kg/min) or dopamine (1–48 μg/kg/min) produced dose-related dilation of the renal vasculature, resulting in increased renal perfusion. Maximum decreases in renal vascular resistance produced by SK&F 38393 and dopamine were 19 ± 4 and 36 ± 5%, respectively, and the concomitant increments in renal blood flow were 27 ± 6 and 62 ± 8%. High cumulative doses of dopamine increased mean arterial blood pressure (25 ± 7%) and cardiac rate (52 ± 7%), while SK&F 38393 produced only an increase in pressure (17 ± 4%). The relative lack of efficacy of SK&F 38393 on alpha- and beta-adrenergic receptors was confirmed in isolated rabbit aortic rings and in right atria and paced papillary muscles of guinea pigs. SK&F 38393 (650 μg/kg, i.v.) produced significant renal effects for 65–75 min, whereas the activity of an approximately equieffective dose of dopamine (30 μg/kg, i.v.) was limited to the period of administration. Pretreatment of dogs with a maximally effective renal vasodilator dose of SK&F 38393 (650 μg/kg, i.v.) did not attenuate the subsequent renal vascular activity of dopamine; decreases in renal vascular resistance produced by the two drugs were entirely additive. Metoclopramide (10 mg/kg, i.v.) in dogs pretreated with phenoxybenzamine (3 mg/kg, i.v.) produced an approximate 10-fold parallel rightward displacement of the renal vascular dose-response curves to SK&F 38393 and dopamine, indicating competitive antagonism. These findings demonstrate that SK&F 38393 is a long-lasting renal dopamine receptor agonist whose activity is submaximal, relative to dopamine itself. A possible explanation for this difference in the maximum renal vasodilating effect is suggested, based on differential activity at pre- and post-synaptic dopamine receptor sites.