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Effects of fenoldopam, a specific dopamine receptor agonist, on blood pressure and left ventricular function in systemic hypertension

Effects of fenoldopam, a specific dopamine receptor agonist, on blood pressure and left ventricular function in systemic hypertension

British Journal of Clinical Pharmacology 24(6): 721-727

ISSN/ISBN: 0306-5251

PMID: 2894216

DOI: 10.1111/j.1365-2125.1987.tb03237.x

1. The effects of fenoldopam, an orally active, specific dopamine-1 receptor agonist, were studied in eleven patients with essential hypertension, using intra-arterial blood pressure recording and equilibrium gated radionuclide angiography. 2. A single dose of fenoldopam 100 mg produced a fall in blood pressure (BP) starting after 20 min. The maximum BP reduction (23/25 mm Hg) occurred after 50 min and was accompanied by a heart rate (HR) increase of 10 beats min-1. The acute effects on BP lasted for 130 min. 3. After 8 weeks of fenoldopam 100 mg, twice daily, only a small, statistically insignificant, hypotensive effect was still apparent after each dose of drug. The duration of the effect was too short to be clinically useful. Tilt-testing produced a BP fall of 24/14 mm Hg and a HR increase of 17 beats min-1. Three patients experienced symptoms of postural hypotension during the study. 4. The drug attenuated the blood pressure rise produced by dynamic cycle exercise and isometric hand grip. 5. Acute administration of fenoldopam increased the left ventricular ejection fraction from 61% to 71% (P < 0.005) and increased the peak filling rate from 2.52 to 3.86 end diastolic vol s-1 (P < 0.002). After chronic fenoldopam administration, the left ventricular ejection fraction was 65% (P = NS) pre-dose, rising to 69% (P < 0.02) post-dose and the peak filling rate was increased from 2.7 to 3.38 end diastolic vol s-1 (P < 0.01) 60 min post-dose. There was also a significant increase of the first one-third filling fraction from 0.24 to 0.47 (P < 0.01) pre-dose, indicating improved diastolic function. 6. Although the duration of action of this formulation of fenoldopam is too short to recommend it for clinical use, a slow-release preparation would merit further investigation for treatment of hypertension and heart failure.

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Accession: 005304065

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