[Some mechanisms of the development of endothelial disfunction in aging]

Taking into consideration age-related changes in endothelium, the ability of endothelium to produce vasoactive substances has been studied in healthy subjects of various age. Under experimental conditions, the activity of constitutive and inducible NO-synthase has been studied as well. The clinical part of the study involved investigation of 38 healthy subjects aged 60-79. The study has been designed to investigate vasomotor function of the endothelium, the levels of endothelin-1, NO2, prostacyclin, thromboxan, the level of adhesive molecules and inhibitor of tissue plasminogen activator. The levels of endothelial and inducible NO-synthases in tissues of the myocardium and the aorta has been investigated in healthy rats of various age. The data obtained show a decrease in the production of relaxation factors: NO and prostacyclin with aging. An important mechanism of deterioration of NO-synthesizing function of the endothelium is a decrease in endothelial NOS activity. The synthesis of endothelial vasoconstricting agents increased with ageing. This in combination with decreased production of vasodilating substances results in deterioration of defence properties of the endothelium. The increase in titer of adhesive molecules and inhibitors of tissue plasminogen activator testifies to age-dependent deterioration of anti-inflammatory and antithrombotic activities of the endothelium.