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

Hypertension. 2001 Aug;38(2):274-9. doi: 10.1161/01.hyp.38.2.274.


Age-related endothelial dysfunction could be caused by an alteration in the L-arginine-NO system and the production of oxidative stress in both normotensive and hypertensive individuals. In 47 normotensive subjects and 49 patients with essential hypertension, we evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial sodium nitroprusside (1, 2, and 4 microg/100 mL per minute) and acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 microg/100 mL per minute), an endothelium-independent vasodilator and an endothelium-dependent vasodilator, respectively. Acetylcholine was repeated in the presence of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 100 microg/100 mL per minute), the antioxidant vitamin C (8 mg/100 mL per minute), or both. Vasodilation to acetylcholine, but not to sodium nitroprusside, was lower (P<0.01) in hypertensive patients compared with control subjects. Moreover, in both groups, endothelium-dependent vasodilation declined with aging. In normotensive subjects, the inhibiting effect of L-NMMA on response to acetylcholine decreased in parallel with advancing age, whereas vitamin C increased vasodilation to acetylcholine in only 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-dependent 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-related reduction in endothelium-dependent vasodilation. These alterations are similar but anticipated in hypertensive patients compared with normotensive subjects.

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Age Factors*
  • Aged
  • Ascorbic Acid / pharmacology
  • Drug Antagonism
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Female
  • Forearm / blood supply
  • Humans
  • Hypertension / etiology*
  • Hypertension / metabolism*
  • Male
  • Middle Aged
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroprusside / pharmacology
  • Oxidative Stress*
  • Regional Blood Flow / drug effects
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Vasodilator Agents
  • Nitroprusside
  • omega-N-Methylarginine
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Acetylcholine
  • Ascorbic Acid