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(Hypertension. 2002;39:513.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Excess Norepinephrine Impairs Both Endothelium-Dependent and -Independent Vasodilation in Patients With Pheochromocytoma

Yukihito Higashi; Shota Sasaki; Keigo Nakagawa; Masashi Kimura; Satoshi Sasaki; Kensuke Noma; Hideo Matsuura; Keiko Hara; Chikara Goto; Tetsuya Oshima; Kazuaki Chayama

From the First Department of Internal Medicine (Y.H., Sh.S., K.Na., M.K., Sa.S., K.No., K.H., H.M., K.C.), Division of Physical Therapy, Institute of Health Sciences (C.G.), and the Department of Clinical Laboratory Medicine (T.O.), Faculty of Medicine, Hiroshima University, Japan.

Correspondence to Yukihito Higashi, MD, PhD, FAHA, Division of Hypertension and Cardiology, First Department of Internal Medicine, Faculty of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. E-mail yhigashi{at}hiroshima-u.ac.jp

Abstract— There is little information concerning the interaction of nitric oxide and norepinephrine (NE) on endothelial function in humans. The purpose of this study was to determine whether endothelial function is impaired by NE secreted from patients with pheochromocytoma (pheo) and whether surgical resection of the tumor improves endothelial function in these patients. We evaluated the forearm blood flow (FBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after adrenalectomy in 8 pheo patients, 20 normotensive subjects, and 20 patients with essential hypertension. FBF was measured using a mercury-filled silastic strain-gauge plethysmograph. The FBF response to ACh was the greatest in normotensive subjects and the least in pheo patients. The FBF response to ISDN was significantly less in pheo patients than in the other 2 groups, which had similar responses to ISDN. Adrenalectomy significantly decreased plasma and urinary NE, systolic and diastolic blood pressures, heart rate, and forearm vascular resistance. After adrenalectomy, FBF responses to both ACh and ISDN were enhanced in all pheo patients. The ratio of maximal ACh-stimulated FBF to maximal ISDN-stimulated FBF was significantly higher after adrenalectomy than before adrenalectomy (2.1±0.4 versus 1.1±0.1; P<0.05). The increase in maximal FBF response to ACh correlated significantly with the decrease in urinary excretion of NE (r=-0.62, P<0.01). These findings suggest that excess NE from pheo may predominately impair endothelium-dependent vasodilation in humans.

Key Words: pheochromocytoma • norepinephrine • nitric oxide • acetylcholine • endothelial function • hypertension, essential

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