Abstract
Recent development of and studies on fenoldopam prodrugs have shown their prolonged hemodynamic effects. This study was carried out in order to examine the effect of a fenoldopam prodrug on renal function in rats. In the present study we administered SK&F R-105058, the 4′,7,8-tris-N-ethyl carbamate ester of R-fenoldopam, at a dose of 30 μg/kg/min intravenously to the anesthetized rats. This prodrug produced long-lasting increases in water and sodium excretion after termination of the 30-min drug infusion with minimum changes in hemodynamic parameters. The diuresis and natriuresis were attenuated in the presence of a selective DA1 receptor antagonist SCH 23390. Therefore, it is suggested that production of fenoldopam from its precursor drug SK&F R-105058 caused these prolonged renal effects, which were mediated via the activation of DA1 receptors located on renal tubules. © 1992 Wiley-Liss, Inc.
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