Regional haemodynamic 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-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.
Drieman
J C
JC
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
van Kan
F J
FJ
Thijssen
H H
HH
van Essen
H
H
Smits
J F
JF
Struijker Boudier
H A
HA
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D005990:Glycerol / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects
D007980:Levodopa; C017342:gamma-glutamyl DOPA; D004295:Dihydroxyphenylalanine; D005990:Glycerol; D004298:Dopamine