Background: Nitric oxide belongs to the most important factors influencing structural and functional properties of vessel wall. Both genetic and environmental factors may influence its metabolism. The aim of this study was to explore whether two common polymorphisms of endothelial nitric synthase (eNOS) may, jointly with smoking, influence the stiffness of large arteries, quantified by pulse wave velocity (PWV).

Methods: One hundred ninety four subjects free of manifest atherosclerosis or chronic cardiovascular pharmacotherapy were selected from population-based post-MONICA study. PWV’s were measured using Sphygmocor® device between carotic and femoral arteries (aortic PWV) and between femoral and tibialis-posterior arteries (peripheral PWV). Two common eNOS polymorphisms, T786C and G894T, were assessed.

Results: Among current smokers (n=70), homo- or heterozygous carriers of T786C mutation (n=42) showed significantly higher peripheral PWV than normal genotype carriers (14.0 vs 10.7 m/sec, p<0.002); the same applied to the carriers of G894T mutation (n=41; 13.9 vs 11.0 m/sec, p<0.015). No differences were found in non-smokers, and neither of the eNOS polymorphisms influenced aortic PWV in our setting.

Conclusion: Genetically determined disorder of nitric oxide metabolism was associated with increased stiffness of peripheral muscular-type arteries in generally healthy, untreated subjects, but only in interaction with active smoking.

Supported by the EU Projects InGenious HyperCare and HyperGenes.