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(Circulation. 1997;96:1847-1852.)
© 1997 American Heart Association, Inc.

Articles

Direct Vascular Effects of Furosemide in Humans

Peter Pickkers, MD; Tom P. J. Dormans, MD; Frans G. M. Russel, PhD; Alun D. Hughes, MD, PhD; Theo Thien, MD, PhD; Nicolaas Schaper, MD, PhD; ; Paul Smits, MD, PhD

From the Division of General Internal Medicine, Department of Medicine (P.P., T.T., P.S.) and Department of Pharmacology (P.P., T.P.J.D., F.G.M.R., P.S.), University of Nijmegen, Netherlands; the Department of Clinical Pharmacology, St Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, UK (A.D.H.); and the Department of Endocrinology, University of Maastricht, Netherlands (N.S.).

Background In humans, hemodynamic changes observed within minutes after systemic administration of furosemide are often referred to as direct vasoactivity. However, these immediate changes do not per se imply a direct vascular effect. We examined the genuine direct vascular effects of furosemide on the human forearm vascular bed and dorsal hand vein.

Methods and Results Forearm blood flow in response to infusion of increasing dosages of furosemide into the brachial artery was recorded by venous occlusion plethysmography. Local plasma concentrations of furosemide reached a maximum of 234±40 µg/mL during the highest infused dose but did not significantly affect the ratio of flow in the infused/noninfused arms. Venous distensibility of a dorsal hand vein was measured with a linear variable differential transformer. During precontraction with norepinephrine, five increasing dosages of furosemide (1 to 100 µg/min) were administered locally. Additional experiments using local administration of indomethacin or N^G-monomethyl-L-arginine (L-NMMA) were carried out to determine whether effects were dependent on local prostaglandin or nitric oxide synthesis, respectively. Also, the effects of systemic administration of furosemide were examined. Local administration of furosemide led to a dose-dependent venorelaxation of 18±6% at the first to 72±16% at the last dose. Indomethacin almost completely abolished furosemide-induced venorelaxation, whereas L-NMMA had no effect. Systemic administration of furosemide resulted in a time-dependent increase of hand vein distensibility, reaching 45±11% after 8 minutes.

Conclusions Furosemide does not exert any direct arterial vasoactivity in the human forearm, even at supratherapeutic concentrations. In contrast, at concentrations estimated to be in the therapeutic range, we observed a dose-dependent direct venodilator effect on the dorsal hand vein that appears to be mediated by local vascular prostaglandin synthesis.

Key Words: furosemide • pharmacology • vasodilation • blood flow • prostaglandins

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