Hyperaggregability and impaired nitric oxide production in platelets from postmenopausal women

• Postmenopausal women present increased platelet reactivity.
• Plasma levels of l-arginine were 32% lower in postmenopausal women.
• Postmenopausal women present reduced levels of platelet production of nitric oxide.
• Intraplatelet antioxidant defense is activated in postmenopausal women.
• These findings may help to explain platelet dysfunction seen in this population.

ObjectiveCardiovascular mortality increases after menopause in women. Nitric oxide is essential for proper platelet function inhibiting its aggregation and maintaining vascular haemostasis. Here, we investigated whether platelet function and intraplatelet l-arginine–nitric oxide pathway are impaired in postmenopausal women.Study designCross-sectional.Main outcomes measuresBlood was collected from 16 premenopausal and 12 postmenopausal women without any additional risk factor for cardiovascular disease. Platelet reactivity was measured by light transmission aggregometry. l-Arginine–nitric oxide pathway was assessed measuring transmembrane l-[3H]-arginine transport, nitric oxide synthase activity by the citrulline assay, and arginase activity by the conversion of l-[14C]arginine to l-[14C]-urea. The activity of antioxidant enzymes was measured by spectrophotometric assays. Protein expression was determined by Western blotting.ResultsPlatelet aggregation was increased in postmenopausal compared to premenopausal women. Postmenopausal women demonstrated reduced plasma levels of l-arginine, a lower nitric oxide synthase activity, similar endothelial and inducible nitric oxide synthase expression, and a compensatory increase in l-arginine transmembrane transport. Arginase expression and activity did not differ between groups. In regard to oxidative stress, no differences between groups were observed NAPDH oxidase subunits expression and protein carbonylation. However, the activity of the antioxidant enzyme superoxide dismutase and catalase protein levels in platelets were higher in postmenopausal women.ConclusionPostmenopausal women present increased platelet reactivity, which may be due to a reduction in intraplatelet nitric oxide synthesis. Platelet hyperaggregability is known to be associated with arterial and venous thromboembolic event; therefore, it may contribute to the heightened risk of cardiovascular adverse events in this population.