Age-related endothelial dysfunction with respect to nitric oxide, endothelium-derived hyperpolarizing factor and cyclooxygenase products

Vascular aging is associated with both structural and functional changes th at can take place at the level of the endothelium, vascular smooth muscle c ells and the extracellular matrix of blood vessels. With regard to the endo thelium, reduced vasodilatation in response to agonists occurs in large con duit arteries as well as in resistance arteries with aging. Reviews concern ing the different hypotheses that may account for this endothelial dysfunct ion have pointed out alterations in the equilibrium between endothelium-der ived relaxing and constricting factors. Thus, a decreased vasorelaxation du e to nitric oxide and, in some arteries, endothelium-derived hyperpolarizin g factor as well as an increased vasoconstriction mediated by cyclooxygenas e products such as thromboxane A? are likely to occur in age-induced impair ment of endothelial vasodilatation. Furthermore, enhanced oxidative stress plays a critical role in the deleterious effect of aging on the endothelium by means of nitric oxide breakdown due to reactive oxygen species. The rel ative contribution of the above phenomenon in age-related endothelial dysfu nction is highly dependent on the species and type of vascular bed.