G L Bakris1, N A Lass, D Glock. 1. Rush University Hypertension Center, Department of Preventive Medicine, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612, USA. gbakris@rush.edu
Abstract
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). CONCLUSION: 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.
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). CONCLUSION: 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.
Authors: Thomas M Kitzler; Aala Jaberi; Gerald Sendlhofer; Peter Rehak; Christian Binder; Eva Petnehazy; Rudolf Stacher; Peter Kotanko Journal: Wien Klin Wochenschr Date: 2012-04-24 Impact factor: 1.704
Authors: Ricardo M Heguilén; Amador A Liste; Miguel Payaslian; Martin Gabriel Ortemberg; Lautaro Martin Albarracín; Amelia Rita Bernasconi Journal: Clin Exp Nephrol Date: 2012-11-10 Impact factor: 2.801