Hemodynamic, renal, and neurohumoral effects of a selective oral DA1 receptor agonist (fenoldopam) in patients with congestive heart failure

Gary S Francis, Bruce C. Wilson, Tom S. Rector

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29 Scopus citations

Abstract

Fenoldopam mesylate (SK&F 82526-J) is a novel benzazepine derivative. It has selective agonist activity at post-junctional (DA1) vascular dopaminergic receptors, which normally subserve renal artery vasodilation. Previous studies in normal subjects and in patients with hyportension indicate that fenoldopam increases renal blood flow and promotes a sodium diuresis. Drug efficacy was clinically evaluated in eight patients with chronic congestive heart failure (CHF) after a single oral dose of 100 mg of fenoldopam and following 3 days of therapy (100 mg four times daily). Stroke volume index acutely increased from 26 ± 7 (mean ± SD) to 30 ± 4 ml/beat/m2 (p < 0.05) and left ventricular filling pressure decreased from 26 ± 13 to 23 ± 11 mm Hg (p < 0.05). Systemic vascular resistance decreased from 1513 ± 159 to 1128 ± 319 (p < 0.05). Hemodynamic changes were seen as early as 30 minutes following fenoldopam and returned to control levels by 4 hours. Forearm blood flow, hepatic blood flow, and venous capacitance did not significantly change acutely, but renal blood flow index was significantly reduced (34 ± 4 to 30 ± 3 min-1 × 1000, p < 0.01). Plasma norepinephrine, plasma renin activity, plasma arginine vasopressin, and plasma aldosterone did not significantly change acutely. After 3 days of treatment, 100 mg of fenoldopam again reduced the renal blood flow index (35 ± 7 to 26 ± 7 min-1 × 1000, p < 0.01) and tended to increase plasma renin activity (11.7 ± 8 to 21.2 ± 19.4 ng/ml/hr, p = NS). Three days of fenoldopam, 100 mg four times daily, did not result in a sodium diuresis. We conclude that fenoldopam is a short-acting, orally effective vasodilator in patients with CHF that increases stroke volume and reduces filling pressure. However, contrary to its effects in normal subjects and in patients with hypertension, oral fenoldopam in this dose may reduce renal blood flow and it fails to promote a sodium diuresis in patients with CHF, thereby possibly limiting its utility.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalAmerican Heart Journal
Volume116
Issue number2 PART 1
DOIs
StatePublished - Aug 1988

Bibliographical note

Funding Information:
From the Department of Medicine, Veterans Administration Center and the University of Minnesota Medical School. Computational assistance was provided by the CLINFO Project, funded Grant RR.400, Division of Research Resources, National Institutes Health, Bethesda, Md. This project was funded in part by a research from Smith Kline & French Laboratories, Philadelphia, Pa., and supported by the Veterans Administration Research Service. for publication Feb. 16, 1988; accepted Apr. 1, 1988. Reprint requests: Gary S. Francis, MD, Cardiovascular VA Medical Center, Minneapolis, MN 55417.

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