REGIONAL HEMODYNAMIC-EFFECTS OF DOPAMINE AND ITS PRODRUGS L-DOPA AND GLUDOPA IN THE RAT AND IN THE GLYCEROL-TREATED RAT AS A MODEL FOR ACUTE-RENAL-FAILURE

1 In this study the renal selectivity of dopamine and its prodrugs L-d opa and gludopa, with respect to their effects on regional blood flow, vascular resistance and central haemodynamics was investigated in nor mal rats and in rats with glycerol-induced acute renal failure (ARF). 2 In normal, anaesthetized rats, dopamine as well as its prodrugs caus ed 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 press ure and heart rate were affected at the highest dose only. 3 Administr ation 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-i nduced reduction of renal flow and increase in RR were significantly a ttenuated. 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 treat ments used. 4 The results indicate that gludopa is not renally selecti ve at a pharmacodynamic level in normal, anaesthetized rats. Contrary to this, a low dose of gludopa does cause a renal selective vasodilata tion and reduction of RR in rats with glycerol-induced ARF. This diffe rence could be explained by a difference in renal vascular tone betwee n normal rats and glycerol-induced ARF rats. A high dose of gludopa do es 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.