Change in Augmentation Index during NOS Inhibition, an Index of Basal NO Production, Is an Independent Determinant of Large-Artery Function

BACKGROUND/AIMS: Arterial wave reflection, measured as augmentation index (AIx), and central pulse pressure (PP) closely predict cardiovascular events. We hypothesized that basal nitric oxide (NO) production would be a determinant of AIx and central PP. METHODS: AIx and central PP were assessed at baseline by pulse wave analysis in 86 male subjects across a wide range of age, blood pressure and lipid values. The basal NO production in the cardiovascular system was then determined as change in AIx during NO synthase blockade with N(G)-monomethyl-L-arginine (L-NMMA, 3.25 mg/kg). RESULTS: AIx increased from 17.5 ± 14.6 to 23.1 ± 14.2 during L-NMMA infusion (p < 0.001). The increase in AIx during NO synthase blockade, an index of basal NO production, was inversely related to baseline central AIx and PP, and positively to PP amplification. Multiple linear regression analyses disclosed that in addition to age and mean blood pressure, change of AIx to L-NMMA is a strong and independent determinant of baseline central AIx, central PP and PP amplification. CONCLUSION: Greater change of AIx to L-NMMA, an index of basal NO production, is associated with better large-artery function. Therefore, therapeutic interventions which increase the basal NO production might be particularly effective in reducing cardiovascular risk.