Age-related reduction of NO availability and oxidative stress in humans

Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normot ensive and hypertensive individuals. In 47 normotensive subjects and 49 pat ients with essential hypertension, we evaluated forearm blood flow (by stra in-gauge plethysmography) modifications induced by intrabrachial sodium nit roprusside (1, 2, and 4 mug/100 mL per minute) and acetylcholine (0.15, 0.4 5, 1.5, 4.5, and 15 mug/100 mL per minute), an endothelium-independent vaso dilator and an endothelium-dependent vasodilator, respectively. Acetylcholi ne was repeated in the presence of the NO synthase inhibitor N-G-monomethyl -L-arginine (L-NMMA, 100 mug/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not t o sodium nitroprusside, was lower (P<0.01) in hypertensive patients compare d with control subjects. Moreover, in both groups, endothelium-dependent va sodilation declined with aging. In normotensive subjects, the inhibiting ef fect of L-NMMA on response to acetylcholine decreased in parallel with adva ncing age, whereas vitamin C increased vasodilation to acetylcholine in onl y the oldest group (age >60 years). In young hypertensive patients (age <30 years), vasodilation to acetylcholine was sensitive to L-NMMA, whereas in hypertensive patients age >30 years, vitamin C enhanced endothelium-depende nt vasodilation and restored the inhibiting effect of L-NMMA on response to acetylcholine. In normotensive individuals, an earlier primary dysfunction of the NO system and a later production of oxidative stress cause age-rela ted reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.