Selective peripheral dopamine-1 receptor stimulation with fenoldopam in human essential hypertension.
Open Access
- 1 December 1984
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 74 (6), 2198-2207
- https://doi.org/10.1172/jci111646
Abstract
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. We studied SKF 82526-J in 10 patients with essential hypertension and five normal control subjects on constant 150-meq sodium, 60 meq potassium intake. In the hypertensive patients, during a 6-d placebo period supine blood pressure and heart rate were stable at 156 +/- 6/105 +/- 4 mmHg and 76 +/- 5 beats/min, respectively. In response to a single oral dose of 100 mg of SKF 82526-J, supine blood pressure decreased to a nadir of 141 +/- 5/89 +/- 8 mmHg (P less than 0.0001) at 90 min and remained decreased at 145 +/- 6/99 +/- 3 mmHg (P less than 0.0001) at 4 h. Heart rate increased to 91 +/- 5 beats/min (P less than 0.002), but returned to control levels (82 +/- 5 beats/min) at 4 h. Renal blood flow increased from 371 +/- 57 to a peak of 659 +/- 104 ml/min and renal vascular resistance fell from 34 +/- 5 to 19 +/- 2 dyn sec cm-5 X 10(3) (P less than 0.01). Urine volume, sodium and fractional sodium excretion, and plasma renin activity were increased as a result of SKF 82526-J administration. During the ensuing 3 wk of SKF 82526-J, blood pressure remained decreased and returned to control levels after placebo administration. In contrast, in normal subjects SKF 82526-J administration was associated with a small transient reduction in diastolic pressure only. These results suggest that reduced dopaminergic activity expressed at the peripheral DA-1 receptor may contribute to the pathophysiology and/or maintenance of increased blood pressure in essential hypertension. In addition, the results suggest that peripheral DA-1 receptor stimulation with SKF 82526-J may be efficacious in the treatment of human essential hypertension.This publication has 26 references indexed in Scilit:
- The Dopamine Agonist Bromocriptine Induces Hypotension by Venous and Arteriolar DilationJournal of Cardiovascular Pharmacology, 1984
- THE RENAL VASCULATURE IN EARLY ESSENTIAL HYPERTENSIONMedicine, 1978
- RENAL VASCULAR TONE IN ESSENTIAL AND SECONDARY HYPERTENSIONMedicine, 1975
- Single-Antibody Technique for Radioimmunoassay of Cortisol in Unextracted Serum or PlasmaClinical Chemistry, 1974
- A Homologous Radioimmunoassay for Human Prolactin1Journal of Clinical Endocrinology & Metabolism, 1973
- Cardiovascular and renal actions of dopamine: potential clinical applications.1972
- Autoregulation of the total systemic circulation and its relation to control of cardiac output and arterial pressure.1971
- Effects of Dopamine in Man: Augmentation of Sodium Excretion, Glomerular Filtration Rate, and Renal Plasma Flow*JCI Insight, 1964
- GENERAL AND REGIONAL HAEMODYNAMIC PATTERN UNDERLYING ESSENTIAL HYPERTENSION1962
- A RAPID METHOD FOR THE DETERMINATION OF PARA-AMINOHIPPURIC ACID IN KIDNEY FUNCTION TESTS1951