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

Br J Pharmacol. 1994 Apr;111(4):1117-22. doi: 10.1111/j.1476-5381.1994.tb14860.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / physiopathology*
  • Animals
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / pharmacology
  • Dopamine / pharmacology*
  • Glycerol / pharmacology
  • Hemodynamics / drug effects
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Levodopa / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Renal Circulation / drug effects

Substances

  • Levodopa
  • gamma-glutamyl DOPA
  • Dihydroxyphenylalanine
  • Glycerol
  • Dopamine