Fenoldopam is a racemic mixture with the R-isomer responsible for the biological activity. The R-isomer has approximately 250-fold higher affinity for D1-like receptors than does the S-isomer. Fenoldopam is a dopamine (D1) receptor agonist that results in decreased peripheral vascular resistance primarily in renal capillary beds, thus promoting increased renal blood flow, natriuresis, and diuresis. Fenoldopam has minimal adrenergic effects. Fenoldopam is used as an antihypertensive agent postoperatively and also intravenously to treat hypertensive crises. Since fenoldopam is the only intravenous agent that improves renal perfusion, it may be beneficial in hypertensive patients with chronic kidney disease. Fenoldopam administration is via a continuous intravenous (IV) infusion using an infusion pump. In arteries, the tunica media is composed of smooth muscle cells activated by various neurotransmitters, hormones, and mechanical perturbations. The contraction and relaxation of vascular smooth muscle are the mechanisms by which changes in systemic vascular resistance (SVR) occur. Dopamine D1 receptors are located in the tunica media of arteries and exert their effects through a G-alpha stimulatory second messenger system. Upon ligand binding such as fenoldopam binding to D1-receptors, the alpha subunit dissociates from the intracellular domain of the transmembrane receptor and activates adenylate cyclase (AC). AC subsequently converts ATP to cyclic adenosine monophosphate (cAMP). All downstream effects get mediated by cAMP, the chief second messenger in this pathway. Inside the cell, cAMP activates protein kinase A (PKA). PKA phosphorylates MLCK, thus causing its inactivation. Since myosin cannot undergo phosphorylated by MLCK, the cross-bridge formation between myosin and actin does not occur, rendering the arterial smooth muscle cell unable to contract. The result is the dilation of arteries producing decreased SVR, increased renal blood flow, natriuresis, and diuresis. These pharmacologic effects result in a decrease in blood pressure.

Fenoldopam Mechanism of Action Pathway References