title: Excess norepinephrine impairs both endothelium-dependent and -independent vasodilation in patients with pheochromocytoma.
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 predominantly impair endothelium-dependent vasodilation in humans.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Hiroshima University, Japan. yhigashi@hiroshima-u.ac.jp
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Shota
authors.initials: S
authors.lastname: Sasaki
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuura
authors.forename: Keiko
authors.initials: K
authors.lastname: Hara
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oshima
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000315:Adrenalectomy / Q000009:adverse effects; D000328:Adult; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010673:Pheochromocytoma / Q000473:pathology / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009638:Norepinephrine