title: Reduced nitric oxide levels in acromegaly: cardiovascular implications.
abstract: Acromegaly is characterized by major cardiovascular alterations. Although the underlying mechanisms of these vascular modifications have not been elucidated, recent studies have focused on endothelial dysfunction. Nitric oxide (NO) may contribute to increased vascular resistance, reduced platelet aggregation, inhibition of smooth muscle cell proliferation, and reduction of lipoxygenase activity. At present, no data on NO production in acromegalics are available. The aim of this study was to evaluate the effect of high levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) present in acromegaly on NO pathway to investigate the role played by this molecule in the cardiovascular changes experienced by these patients. We studied 13 acromegalics and 12 sex- and age-matched normotensive controls. Platelet NO levels were measured in the supernatant of lysed platelets. Endothelial NO synthase (eNOS) was determined by Western blot analysis of platelets. NO concentrations were significantly reduced in patients (p<0.0001). There were no differences between male and female patients, nor were platelet NO levels and the presence/absence of hypertension related in acromegalics; by contrast, NO concentrations inversely correlated with GH (p=0.03) and IGF-1 (p=0.04) levels, and with disease duration (p=0.04). eNOS protein concentrations were significantly reduced in the platelets of patients compared with controls (p<0.0001). This study demonstrates for the first time a strong reduction in platelet NO concentrations in acromegalic patients due to reduced eNOS expression. Moreover the inverse correlation of NO levels with GH, IGF-1 and disease duration suggests that reduced levels of platelet NO linked to GH excess may contribute to the vascular alterations affecting patients with acromegaly.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Università Politecnica delle Marche, Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ronconi
authors.forename: Gilberta
authors.initials: G
authors.lastname: Giacchetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Mariniello
authors.forename: Andrea
authors.initials: A
authors.lastname: Camilletti
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.forename: Arianna
authors.initials: A
authors.lastname: Vignini
authors.forename: Laura
authors.initials: L
authors.lastname: Mazzanti
mesh_terms: D000172:Acromegaly / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D002319:Cardiovascular System / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000097:blood; D052250:Nitric Oxide Synthase Type III; D017698:Postmenopause
chemical_list: D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III