Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Dlewati, Abdallah; Lokhandwala, Mustafa F.

doi:10.1002/ddr.430220106

Cited by 12 publications

(6 citation statements)

References 15 publications

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“…As shown in Figure 6C, fenoldopam with a dose of 1 μg/kg/min caused a ~ 30% RBP increase, and the effect plateaued within 5 min after starting the infusion. The increase and the temporal pattern of the RBP response to fenoldopam are consistent with the literature‐reported results measured by the invasive flow probe method in anesthetized dogs 28 . For L‐NAME, the dosage of 25 mg/kg caused a decrease of 55% in RBP 40 min after L‐NAME delivery (Figure 7A).…”

Section: Discussionsupporting

confidence: 90%

“…For fenoldopam treatment, fenoldopam (CORLOPAM, Pfizer) was diluted from 10 mg/mL to 10 ug/ml in saline, and was intravenously infused at a rate of 1 ug/kg/min (volume rate of 0.1 mL/kg/min) via the other tail vein for 40 min. The dose of fenoldopam was similar to the doses tested in previous studies 21,22,28 . For the saline vehicle treatment, a bolus of 2.5 mL/kg saline was intravenously delivered via a tail vein catheter over 3 min.…”

Section: Methodsmentioning

confidence: 99%

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Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

et al. 2021

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Kidney diseases such as acute kidney injury, diabetic nephropathy and chronic kidney disease (CKD) are related to dysfunctions of the microvasculature in the kidney causing a decrease in renal blood perfusion (RBP). Pharmacological intervention to improve the function of the microvasculature is a viable strategy for the potential treatment of these diseases. The measurement of RBP is a reliable biomarker to evaluate the efficacy of pharmacological agents' actions on the microvasculature, and measurement of RBP responses to different pharmacological agents can also help elucidate the mechanism of hemodynamic regulation in the kidney. Magnetic resonance imaging (MRI) with flow‐sensitive alternating inversion recovery (FAIR) arterial spin labeling (ASL) has been used to measure RBP in humans and animals. However, artifacts caused by respiratory and peristaltic motions limit the potential of FAIR ASL in drug discovery and kidney research. In this study, the combined anesthesia protocol of inactin with a low dose of isoflurane was used to fully suppress peristalsis in rats, which were ventilated with an MRI‐synchronized ventilator. FAIR ASL data were acquired in eight axial slices using a single‐shot, gradient‐echo, echo‐planar imaging (EPI) sequence. The artifacts in the FAIR ASL RBP measurement due to respiratory and peristaltic motions were substantially eliminated. The RBP responses to fenoldopam and L‐NAME were measured, and the increase and decrease in RBP caused by fenoldopam and L‐NAME, respectively, were robustly observed. To further validate FAIR ASL, the renal blood flow (RBF) responses to the same agents were measured by an invasive perivascular flow probe method. The pharmacological agent‐induced responses in RBP and RBF are similar. This indicates that FAIR ASL has the sensitivity to measure pharmacologically induced changes in RBP. FAIR ASL with multislice EPI can be a valuable tool for supporting drug discovery, and for elucidating the mechanism of hemodynamic regulation in kidneys.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

et al. 2021

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“…To maintain the independence of this work, no financial support or donated fenoldopam a was requested of the manufacturer. Dosages employed in dose‐response experiments were based on dose‐response studies previously conducted in dogs and humans whereby fenoldopam dosages effective in inducing diuresis ranged from 0.125 to 1.0 μg/kg/min 9,12,13 . The dosage of the DA‐1 antagonist, SCH23390, b was derived from experiments in dogs and cats 14,15 .…”

Section: Methodsmentioning

confidence: 99%

Diuretic effects of fenoldopam in healthy cats

Simmons¹,

Wohl²,

Schwartz

et al. 2006

J Vet Emergen Crit Care

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Objective:To determine the effect of fenoldopam infusion on urine output, sodium excretion, creatinine clearance, and indirect blood pressure in healthy cats. Design: Prospective study. Setting: Veterinary medical teaching hospital. Animals: Eight purpose-bred cats, 2-4 years old. Interventions: None. Measurements: Urine output was measured hourly for 12 hours before and after fenoldopam administration. Sodium excretion, modified creatinine clearance, and fractional sodium excretion were measured before and following fenoldopam administration. Urine specific gravity, central venous pressure, and systolic blood pressure were measured every 4 hours during the experiment.Main results: Compared with pre-infusion values, urine output, sodium excretion, and fractional excretion of sodium increased significantly 6 hours after initiation of fenoldopam infusion. This increase was sustained throughout the observation period. The modified creatinine clearance decreased significantly following 2 hours of fenoldopam infusion, but increased significantly by 6 hours after infusion, the time of peak urine output. Changes in urine specific gravity mirrored changes in fractional sodium excretion, whereas the central venous pressure mirrored changes in modified creatinine clearance. The diuretic effect in cats was prevented when a dopamine receptor blocking agent was administered before fenoldopam infusion. Conclusion: Fenoldopam at a dose of 0.5 mg/kg/min induces diuresis in cats in a delayed manner. This increase appears to be due, in part, to dopamine receptor-induced natriuresis. Changes in glomerular filtration rate may also occur. (J Vet Emerg Crit Care 2006; 16(2): 96-103)

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“…infusion of fenoldopam significantly increased renal blood flow and decreased renal vascular resistance [17–19]. In dogs, low doses of fenoldopam (0.125 µg kg −1 min −1 ) that did not decrease arterial pressure, produced diuresis and natriuresis when administered i.v [20]. In dogs with spontaneous renal failure, as well as those with normal renal function, renal plasma flow increased by 100% after i.v.…”

Section: Introductionmentioning

confidence: 99%

The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs

et al. 2000

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Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of fenoldopam (0.1 microg kg-1 min-1) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or fenoldopam (0.1 microg kg-1 min-1) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of fenoldopam (0.1 microg kg-1 min-1). Creatinine clearance (2.03 +/- 0.5-2.45 +/- 0.3 mL min-1 kg-1 (mean +/- SD)), urine output (0.23 +/- 0.16-0.35 +/- 0.23 mL min-1 (mean +/- SD)), and fractional excretion of sodium (0.7 +/- 0.52-1.3 +/- 0.73% (mean +/- SD)) increased (P < 0.05), following commencement of the fenoldopam infusion. Fractional excretion of sodium (1.2 +/- 0.7% (mean +/- SD)) and urine output (0. 36 +/- 0.21 mL min-1 (mean +/- SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the fenoldopam infusion was commenced (145 +/- 43.3-161 +/- 39. 2 mL min-1 (mean +/- SD)) and remained greater than baseline during the aortic cross-clamping period (152 +/- 44 mL min-1 (mean +/- SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion fenoldopam (0.1 microg kg-1 min-1) may have renoprotective effects which persist during infrarenal aortic cross clamping.

show abstract

Dose‐response analysis of the effects of fenoldopam, dopamine‐1 receptor agonist, on renal function

Cited by 12 publications

References 15 publications

Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

Robust arterial spin labeling MRI measurement of pharmacologically induced perfusion change in rat kidneys

Diuretic effects of fenoldopam in healthy cats

The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs

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