Disease relevance of fenoldopam

• Selective peripheral dopamine-1 receptor stimulation with fenoldopam in human essential hypertension [1].
• We conclude that the acute administration of fenoldopam did not improve renal hemodynamics or function in patients with cirrhosis and ascites [2].
• Rats infused for 24-hours with 5-100 micrograms/kg/min of fenoldopam had lesions of renal and splanchnic arteries characterized by medial necrosis and hemorrhage [3].
• Hemodynamic effects of an oral dopamine receptor agonist (fenoldopam) in patients with congestive heart failure [4].
• Thus, fenoldopam is safe and effective as a parenteral monotherapy in patients with severe essential and renovascular hypertension [5].

Psychiatry related information on fenoldopam

• Simultaneous bilateral infusion of various dose combinations of fenoldopam (2.5-10 micrograms) and quinpirole (5-20 micrograms) elicited dramatic increases in stereotyped behaviors relative to the effects produced by corresponding doses of each drug alone [6].
• In nephrectomized rats, the blood pressure effects of fenoldopam (assessed as area under the infusion time-response curve) were more pronounced than in sham-operated controls [7].

High impact information on fenoldopam

• In the cytosol, pramipexole and fenoldopam increased expression of both PLC beta 1 and PLC gamma 1 [8].
• Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged [8].
• To determine if catecholamines differentially regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the renal artery of anesthetized rats [8].
• SKF 82526-J, or fenoldopam, a benzazepine derivative, is a selective dopamine-1 (DA-1) agonist devoid of activity at dopamine-2, alpha- or beta-adrenergic receptors [1].
• This protective effect of fenoldopam was increased further during infusion of NaF or cholera toxin (-18% or -19% decrease in renal blood flow) [9].

Chemical compound and disease context of fenoldopam

• Immediate hemodynamic effects of a dopamine-receptor agonist (fenoldopam) in patients with essential hypertension [10].
• Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension [11].
• We studied the renal effects of intravenous administration of fenoldopam mesylate, a dopamine-1 agonist, vs sodium nitroprusside following acute reduction of blood pressure (BP) in 11 patients with severe hypertension (supine BP, 168/124 to 252/135 mm Hg) [12].
• Since CIN accounts for a significant increase of hospital-acquired renal failure, length of stay and mortality, several additive strategies to prevent CIN are presently advocated, including N-acetylcysteine (NAC), sodium bicarbonate, theophylline or fenoldopam, and peri-procedural hemofiltration/hemodialysis [13].
• The detection of toxic levels of thiocyanate in two patients treated with nitroprusside, however, shows that fenoldopam might be preferable for the control of a hypertensive crisis or severe hypertension in patients with decreased renal function [14].

Biological context of fenoldopam

• Pronounced enhancement of renal function in spite of blood pressure reduction suggests that fenoldopam might have a special role in the treatment of patients with hypertension and renal impairment [15].
• Administration of fenoldopam with only DA (1 microgram/kg/min) produced further increase in renal blood flow [16].
• In 10 patients studied during free-water diuresis, fenoldopam increased renal plasma flow by 42%, glomerular filtration rate by 6%, and sodium excretion by 202%, while lowering mean arterial pressure by 12% (all p less than .05) [15].
• In SHRs, fenoldopam failed to attenuate Ang II-mediated vasoconstriction (-45% vs. -44%) [9].
• In LTK- cells stably transfected with rat D1A receptor cDNA, fenoldopam, a D1 agonist, increased phosphatidylinositol 4, 5-bisphosphate hydrolysis in a time-dependent manner [17].

Anatomical context of fenoldopam

• Hepatic, azygos and renal veins were catheterized before and after intravenous administration of fenoldopam, 0.05 micrograms/kg/min for 1 hr and increased to 0.1 micrograms/kg/min for another hour [2].
• Before and after each fenoldopam dose, thermodilution cardiac output, right atrial pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure (PCWP) were measured with a balloon-tipped pulmonary artery catheter, and heart rates and blood pressures were recorded with an automated sphygmomanometer [18].
• Fenoldopam does not cross the blood-brain barrier, which suggests that its hypotensive effect was mediated by peripheral dopamine1 receptors [19].
• Fenoldopam mesylate stimulates adenyl cyclase in porcine ocular trabecular meshwork and raises intraocular pressure in humans [20].
• Fenoldopam may be particularly useful in patients who develop hypertension after coronary artery bypass graft surgery, but further studies are required to confirm its role in hypertensive emergency [21].

Associations of fenoldopam with other chemical compounds

• Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine [16].
• The renal and hemodynamic effects of intravenously administered fenoldopam mesylate, a novel dopamine-1 receptor agonist, were compared with those of sodium nitroprusside in 28 patients (18 male; 26 black, two white; average age, 49 +/- 3 years) with an average blood pressure of 219/137 mm Hg, most of whom presented with acute target organ damage [11].
• The specific dopamine DA1 agonist SKF 82526 caused a dose-dependent inhibition of Na+,K+-ATPase activity, which could be blocked by SCH 23390, a specific DA1 antagonist, and by PKI-(5-24) amide, a specific inhibitor of cAMP-dependent protein kinase [22].
• In contrast, fenoldopam with dobutamine produced greater increments in cardiac contractile force than DA and equivalent increases in renal blood flow as DA [16].
• Thus, these findings show that acute BP reduction with fenoldopam is associated with both a diuresis and natriuresis in severely hypertensive patients while lowering BP with nitroprusside does not predictably alter renal function and causes a moderate expansion in volume [12].

Gene context of fenoldopam

• Reduction in the expression of caveolin-2 with antisense oligonucleotides attenuated the stimulatory effect of fenoldopam on cyclic adenosine monophosphate (cAMP) accumulation [23].
• Inhibition with the PKA blocker H-89 (10 microM) abolished the effect of fenoldopam [24].
• In kidney slices, inhibition of PKC (1 microM chelerythrine) or ERK1/2 (20 microM PD-098089) pathways did not prevent the fenoldopam-induced internalization [24].
• Effects of dopamine DA1-receptor blockade and angiotensin converting enzyme inhibition on the renal actions of fenoldopam in the anaesthetized dog [25].
• We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level [26].

Analytical, diagnostic and therapeutic context of fenoldopam

• 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 [27].
• PURPOSE: To evaluate quantitative Doppler ultrasonography (US) for assessing renal blood flow changes induced with endothelin-1 (ET-1) and fenoldopam mesylate in conscious dogs [28].
• CONCLUSIONS: The study showed that, for the same mean arterial pressure, short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock [29].
• INTERVENTIONS: We randomized patients to a continuous infusion of either fenoldopam (n = 150) at 0.09 microg x kg x min or placebo (n = 150) while in the intensive care unit [30].
• Fenoldopam is a new vasodilator undergoing clinical trials for the treatment of hypertensive emergencies [31].

References