Renal hemodynamics in radiocontrast medium-induced renal dysfunction: A role for dopamine-1 receptors.
BACKGROUND
Radiocontrast medium (RCM) administration induces a transient increase in renal blood flow (RBF), followed by a prolonged vasoconstriction. This vasoconstrictor phase in RBF is accompanied by a decrement in glomerular filtration rate (GFR). Nonselective dopamine (DA) receptor stimulation is known to increase RBF and GFR. Clinical studies, however, fail to demonstrate a renoprotective effect of DA following RCM administration. This lack of renoprotection may relate to nonspecific adrenergic stimulation by DA. The effect of select DA-1 receptor stimulation on renal hemodynamics following RCM administration has not been evaluated.


METHODS
This study tests the hypothesis that selective DA-1 receptor stimulation blunts the declines in RBF and GFR that follow RCM injections, independent of changes in baseline RBF and GFR. Experiments were performed in six anesthetized, volume-depleted dogs. RBF was measured by an electromagnetic flow probe around the renal artery and GFR by inulin clearance. After a 60-minute equilibration period, baseline values of RBF, GFR, and arterial pressure were determined. Two separate intrarenal bolus injections of the ionic RCM Renograffin were then given in the presence of saline infusion. After a 60-minute recovery period, intra-arterial infusions of either the selective DA-1 receptor agonist fenoldopam or the selective DA-1 receptor antagonist Schering 23390 were started in random order, and experiments were repeated.


RESULTS
Neither agent significantly altered baseline values of arterial pressure, RBF, or GFR rate. Fenoldopam prevented reductions in GFR (-17 +/- 2 Deltaml/min, control vs. 2 +/- 1 Deltaml/min, fenoldopam, P < 0.001). Conversely, GFR was further reduced in the presence of Schering 23390 (-15 +/- 2 Deltaml/min, control vs. -23 +/- 1 Deltaml/min, Schering 23390, P < 0.05). Similarly, the maximal reduction in RBF was blunted with fenoldopam (-71 +/- 12 Deltaml/min, control vs. -3 +/- 2 Deltaml/min, fenoldopam, P < 0. 01), whereas Schering 23390 potentiated maximal RBF reductions following the RCM injection (-85 +/- 11 Deltaml/min, control vs. -119 +/- 14 Deltaml/min, Schering 23390, P < 0.05). The duration of recovery from vasoconstriction was also prolonged in the presence of Schering 23390 (342 +/- 35 seconds, control vs. 762 +/- 56 seconds, Schering 23390, P < 0.0001).


CONCLUSIONS
We conclude that selective DA-1 receptor stimulation protects against RCM-mediated decrements in renal hemodynamics, independent of changes in baseline GFR and RBF. Clinical trials are required to examine whether selective DA-1 receptor stimulation may have a role in prophylaxis against nephropathy development in high-risk patients undergoing procedures that require RCM.
Rush University Hypertension Center, Department of Preventive Medicine, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA. gbakris@rush.edu
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Bakris
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D000818:Animals; D003287:Contrast Media / Q000494:pharmacology*; D003974:Diatrizoate Meglumine / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*
D003287:Contrast Media; D017447:Receptors, Dopamine D1; D003974:Diatrizoate Meglumine