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Selective dopamine-1 agonist therapy in severe hypertension: effects of intravenous fenoldopam
W B White1, M J Radford, F M Gonzalez
1Department of Medicine, University of Connecticut School of Medicine, Farmington.
Insights
Intravenous fenoldopam, a dopamine-1 agonist, effectively lowers severe hypertension in patients with essential and renovascular conditions. This therapy also shows preliminary evidence of improving left ventricular function.
Area of Science:
- Cardiology
- Pharmacology
- Nephrology
Background:
- Severe hypertension poses significant risks, necessitating effective therapeutic agents.
- Dopamine-1 (D1) receptor agonists represent a potential class of drugs for managing hypertensive emergencies.
- Understanding the impact of D1 agonists on cardiovascular function is crucial.
Purpose of the Study:
- To evaluate the efficacy and safety of intravenous fenoldopam, a D1 agonist, in patients with severe hypertension.
- To assess the effects of fenoldopam on blood pressure, heart rate, catecholamines, and left ventricular function.
Main Methods:
- A cohort of 18 patients with severe hypertension (diastolic blood pressure > 120 mm Hg) received continuous intravenous fenoldopam infusions.
- Fenoldopam dosage was titrated from 0.1 to 0.9 microgram/kg/min.
- Hemodynamic parameters, catecholamine levels, and left ventricular function were monitored.
Main Results:
- Therapeutic blood pressure goals (< 110 mm Hg diastolic) were achieved in all patients within 1 hour.
- Significant reductions in blood pressure were observed (214/134 to 170/96 mm Hg, p < 0.0001).
- Heart rate increased (p < 0.01), plasma norepinephrine rose, and mild, transient side effects were noted.
Conclusions:
- Intravenous fenoldopam is a safe and effective monotherapy for severe essential and renovascular hypertension.
- Fenoldopam demonstrates potential for improving left ventricular function in hypertensive patients.
- Further research into D1 agonist therapy for hypertension and cardiac function is warranted.
Abstract:
To determine the effects of dopamine-1 agonist therapy in severe hypertension, blood pressure, heart rate, catecholamines and left ventricular function were studied in 18 patients (10 with renal disease) with diastolic blood pressure greater than 120 mm Hg (range 124 to 160) after intravenous fenoldopam therapy. Constant infusions of fenoldopam were titrated upward every 10 to 20 min from an initial dose of 0.1 microgram/kg per min to a maximal dose of 0.9 microgram/kg per min. The therapeutic goal of a supine diastolic blood pressure of less than 110 mm Hg was achieved in every patient within 1 h at an average dose of 0.34 +/- 0.22 microgram/kg per min. Blood pressure decreased from 214/134 +/- 33/10 mm Hg at baseline to 170/96 +/- 29/7 mm Hg (p less than 0.0001) at 3 h, whereas heart rate increased from 77 +/- 23 to 88 +/- 21 beats/min (p less than 0.01). Plasma norepinephrine increased during the fenoldopam infusion; epinephrine and dopamine levels did not change. Two indexes of left ventricular function (end-systolic dimension and isovolumic relaxation time) improved during the fenoldopam infusion, but mitral flow velocities during ventricular filling were unchanged. Side effects of intravenous fenoldopam were mild, transient and associated with the marked vasodilatory properties of the drug. Thus, fenoldopam is safe and effective as a parenteral monotherapy in patients with severe essential and renovascular hypertension. Preliminary data suggest that blood pressure reduction with selective dopamine-1 agonist therapy is accompanied by improved left ventricular function.