Immediate hemodynamic effects of a dopamine-receptor agonist (fenoldopam) in patients with essential hypertension.

Abstract

Systemic, splanchnic, and renal hemodynamics, intravascular volume, and reflexive and endocrine changes were measured before and after a single dose of fenoldopam, a novel antihypertensive agent that acts through stimulation of specific dopamine receptors. A 13% reduction in mean arterial pressure was mediated by a fall in total peripheral resistance associated with an increase in cardiac index, heart rate, stroke volume, left ventricular ejection rate, and circumferential fiber shortening. Renal blood flow increased, thereby reducing the renal vascular resistance by more than 40%. In contrast, splanchnic hemodynamics failed to change. Likewise, there were no changes in intravascular volume, plasma renin activity, or norepinephrine, serum aldosterone, or prolactin levels. Circulation 69, No. 6, 1142No. 6, -1145No. 6, , 1984 THE KIDNEY has been said to be the primary site that both initiates the hypertensive process1 2 and is affected by hypertensive vascular disease. Thus arterial pressure may become elevated by an altered renal excretory "set point" that requires a higher perfusion pressure to excrete its sodium load, perhaps because of afferent glomerular arteriolar constriction.2 3 In contrast, as a result of the systemic arteriolar constriction, blood flow to the kidney may be diminished.`' Therefore a vasodilating agent, preferably with greater effects on the kidney, should be particularly useful in the treatment of patients with essential hypertension.Fenoldopam, a benzazepine derivative, is a novel antihypertensive agent with selective renal vasodilating properties. Preliminary studies in animals9 10 and patients"1 have indicated that it acts through stimulation of specific postsynaptic dopamine receptors in the renal vascular bed. However, unlike dopamine, higher doses of fenoldopam do not seem to increase either blood pressure or heart rate.9 This study was designed to determine the systemic and regional hemodynamic, cardiac, reflexive, and biochemical effects of a single Materials and methodsFourteen patients (10 men and four women) with mild established essential hypertension were included in this study. All had either never received antihypertensive therapy or had therapy discontinued at least 4 weeks before entering the study. Detailed clinical evaluation did not reveal any secondary cause for the hypertension or any concomitant disorders. 12 Each subject provided informed consent to a protocol previously approved by our institution's review committee.All patients had a supine diastolic pressure (phase V of Korotkoff sounds) consistently above 90 mm Hg but not exceeding 120 mm Hg. Systemic and regional hemodynamics together with M mode echocardiograms, electrocardiograms, and blood samples for measurement of plasma renin activity and norepinephrine, serum aldosterone, and prolactin levels were obtained before (after placebo) and 1 hr after the oral administration of fenoldopam (50 [n = 5] or 100 mg [n = 9]). Systemic and regional hemodynamics were determined by methods previously report...

Renal and hemodynamic effects of intravenous fenoldopam versus nitroprusside in severe hypertension.

“…This study confirms and extends previous studies that have demonstrated the antihypertensive efficacy of fenoldopam, both after oral'8-21 and, especially, intravenous1314, 17,19,[22][23][24][25] have shown that intravenous fenoldopam is effective in mild-to-moderate hypertension,14 refractory hypertension (i.e., patients with diastolic blood pressures >115 mm Hg on triple-drug therapy),23 and severe hypertension,172425 but this is the first series to include a majority of patients with accelerated/ malignant hypertension, which is presumably the population in which it will find the widest use. In addition, the present series includes a preponderance of black patients, who comprise a small minority of those previously treated with fenoldopam.17 Indeed, because of the greater frequency of severe hypertension and its complications (including accelerated/malignant hypertension) in blacks,26'27 fenoldopam may be especially useful in such patients, who more commonly have reduced salt and water excretion rates,28 independent of the degree of renal dysfunction.…”

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

“…Increments in HR previously have been observed with orally administered fenoldopam in hypertensive patients. 23 ' 24 Furthermore, in a recent study, we observed that intravenous infusions of fenoldopam in hypertensive patients consistently increased plasma NE levels. 23 Although piribedil is used primarily as a centrally acting DA agonist for the treatment of Parkinson's disease, 26 it also inhibits adrenergic transmission by action on DA 2 receptors.…”

“…23 ' 24 Furthermore, in a recent study, we observed that intravenous infusions of fenoldopam in hypertensive patients consistently increased plasma NE levels. 23 Although piribedil is used primarily as a centrally acting DA agonist for the treatment of Parkinson's disease, 26 it also inhibits adrenergic transmission by action on DA 2 receptors. 18 In the present study, the hypotensive effects of piribedil were completely blocked by domperidone, whereas the bradycardie effect was significantly but not completely antagonized.…”

Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

“…Fenoldopam, a potent agonist at peripheral dopamine1 (DA1)-receptors, has been shown to produce beneficial haemodynamic effects including an improvement in renal plasma flow and a reduction in blood pressure following both intravenous and oral administration (Stote et al, 1983;Ventura et al, 1984). The development of this benzazepine derivative followed the elucidation of the role of dopamine in the regulation of vascular tone and blood pressure (Stoof & Kebabian, 1984;Yeh et al, 1969; Leenders et al, 1984;Langer, 1974 it does not produce such effects in the intact animal because of poor penetration across the blood-brain barrier (Harvey et al, 1985).…”

“…These effects began approximately 45 min after dosing and persisted for 2-3 h. While mean heart rate increased modestly, mean blood pressure was relatively unchanged in these normal subjects. However, in hypertensive patients, fenoldopam is associated with a significant antihypertensive effect (Ventura et al, 1984).…”