1. In this study the renal selectivity of
dopamine and its
prodrugs L-dopa and
gludopa, with respect to their effects on regional blood flow, vascular resistance and central haemodynamics was investigated in normal rats and in rats with
glycerol-induced
acute renal failure (ARF). 2. In normal, anaesthetized rats,
dopamine as well as its
prodrugs caused a dose-dependent reduction of vascular resistance in the kidney (RR), mesentery (MR) and hindquarters (HQR) (dose range:
dopamine: 0.1-5 mumol kg-1 h-1;
L-dopa and
gludopa: 1-200 mumol kg-1 h-1). Blood pressure and heart rate were affected at the highest dose only. 3. Administration of
glycerol induced a preferential renal vasoconstriction; renal blood flow (-60%) and vascular resistance (+190%) were significantly more affected than MR (+40%) and HQR (+60%). This was only ameliorated by a low rate (10 mumol kg-1 h-1) infusion of
gludopa: the
glycerol-induced reduction of renal flow and increase in RR were significantly attenuated. A high dose of
gludopa (100 mumol kg-1 h-1) or any dose of
L-dopa or
dopamine did not induce this beneficial effect. The
glycerol-induced increase in MR and HQR was not attenuated by any of the treatments used. 4. The results indicate that
gludopa is not renally selective at a pharmacodynamic level in normal, anaesthetized rats. Contrary to this, a low dose of
gludopa does cause a renal selective vasodilatation and reduction of RR in rats with
glycerol-induced ARF. This difference could be explained by a difference in renal vascular tone between normal rats and
glycerol-induced ARF rats. A high dose ofgludopa does not cause these renal-selective effects: renal resistance and renal flow are at the same level as following
glycerol and saline. This is probably due to the systemic effects of the released
dopamine.