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(Hypertension. 1999;33:36-43.)
© 1999 American Heart Association, Inc.

Scientific Contributions

A Test of the "Epinephrine Hypothesis" in Humans

David S. Goldstein; Anna Golczynska; John Stuhlmuller; Courtney Holmes; Robert F. Rea; Ehud Grossman; Jacques Lenders

From the Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Md (D.S.G., A.G., C.H.); Food and Drug Administration, Department of Health and Human Services, Rockville, Md (J.S.); Mayo Clinic, Rochester, Minn (R.F.R.); Department of Internal Medicine D, Chaim Sheba Medical Center, Tel Ha-Shomer, Israel (E.G.); and Department of Internal Medicine, St Radboud University Hospital Nijmegen, Nethlerlands (J.L.).

Correspondence to Dr David S. Goldstein, Building 10, Room 6N252, NINDS, NIH, 10 Center Dr MSC-1620, Bethesda, MD 20892-1620. E-mail daveg{at}box-d.nih.gov

Abstract—According to the "epinephrine hypothesis," circulating epinephrine taken up by sympathetic nerves is coreleased with norepinephrine during sympathetic stimulation and binding of coreleased epinephrine to presynaptic ß-adrenoceptors augments exocytotic release of norepinephrine, contributing to high blood pressure. This study examined whether infusion of a physiologically active amount of epinephrine affects subsequent vascular responses and the estimated rate of entry of norepinephrine into regional venous plasma (norepinephrine spillover). Each of 3 experiments included intravenous infusion of ³H-norepinephrine, measurements of forearm vascular resistance, and intra-arterial infusion of epinephrine (3 ng/min per deciliter forearm volume). In experiment 1, subjects underwent lower body negative pressure (LBNP-25 mm Hg) before and after intra-arterial epinephrine; in experiment 2, LBNP and intra-arterial yohimbine before and after intra-arterial epinephrine; and in experiment 3, intravenous nitroprusside before and after intra-arterial epinephrine. In all subjects, intra-arterial epinephrine produced ipsilateral pallor and decreased forearm vascular resistance. Ipsilateral venous epinephrine increased by 10-fold. Epinephrine did not affect forearm vasoconstrictor responses to LBNP or vasodilator responses to intra-arterial yohimbine or intravenous nitroprusside; did not affect venous norepinephrine levels or norepinephrine spillover during LBNP, yohimbine, LBNP during yohimbine, or nitroprusside; and did not increase venous epinephrine levels during any of these manipulations. Loading of forearm sympathetic terminals with epinephrine therefore does not augment subsequent neurogenic vasoconstriction or norepinephrine release in the human forearm in response to sympathetic stimulation. The findings are inconsistent with the epinephrine hypothesis.

Key Words: epinephrine • norepinephrine • nervous system, sympathetic • yohimbine • nitroprusside

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