Genetic polymorphisms of endothelial nitric oxide synthase in children with primary hypertension

Nitric oxide (NO) is the main substance regulating vascular tone. Endothelial dysfunction and decreased production of NO is a well-known phenomenon in adults with cardiovascular disease and especially when concomitant disorders such as diabetes and atherosclerosis are present. However, there are only few data on NO, polymorphisms of endothelial NO synthase (eNOS) and endogenous inhibitors of eNOS in children with primary hypertension. Children with primary hypertension usually are not exposed to other cardiovascular risk factors such as diabetes, nicotinism and clinically evident atherosclerosis. Thus, children with primary hypertension present the first step of development of cardiovascular disease and allow study of pathogenesis of cardiovascular disease not disturbed by influence of other disorders. We discuss findings from studies evaluating polymorphisms of eNOS and especially of G894T polymorphism and endogenous inhibitors of eNOS in hypertensive children and children with cardiovascular risk factors. G894T polymorphism has been established a functional mutation that is associated with a blunted endothelial-dependent vasodilation and is associated with an increased risk of cardiovascular disease and early vascular changes observed especially in young hypertensive subjects. Although there are no data that eNOS polymorphisms are associated with development of PH, there is evidence that eNOS G894T polymorphism is associated with early subclinical arterial injury in early phase of cardiovascular disease, i.e. in adolescents with PH. However, effects of genetic polymorphisms of eNOS may be modified by behavioral and environmental factors.