Reduced nitric oxide levels in acromegaly: cardiovascular implications

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.