1. Basal release of @entity842 from the vascular endothelium maintains a constant vasodilating tone. Impaired @entity842 -mediated vasodilatation has been described in @entity101 and @entity66 . Circulatory diseases account for considerable morbidity and almost half of all deaths in @entity1 over the age of 75 years. 2. We have therefore compared @entity842 -dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, @entity165 and @entity413 , using forearm occlusion venous plethysmography combined with brachial artery infusions of the @entity842 synthase inhibitor, @entity7293 ( @entity7293 ; 1, 2 and 4 mumol/min) with @entity1063 (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary @entity1507 excretion after a controlled 48 h low @entity1507 diet as an index of total body @entity842 production and correlated these changes with forearm blood flow responses to @entity7293 and @entity1063 in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66-82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20-35) years and 131/72 (4/3) mmHg respectively. @entity7293 and @entity1063 produced dose-dependent reductions in forearm blood flow in both groups. @entity7293 (4 mumol/min) produced less vasoconstriction in the elderly than in the young (-37.7 +/- 2.6 versus -48.3 +/- 4.2%; P = 0.017). The mean slope of the @entity7293 dose-response curves in the elderly was significantly less than the younger group (-35.2 +/- 3.1 versus -63.7 +/- 10.6; P = 0.041). @entity1063 , 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (-22.8 +/- 2.9 versus -35.3 +/- 5.0%; P = 0.029) although the slopes of the dose-response curves did not differ significantly. 4. Urinary @entity1507 adjusted for @entity1011 clearance was also significantly higher in the younger group (460.6 +/- 97.7 versus 205.9 +/- 64.8 mumol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of @entity7293 (r = 0.5, P = 0.046). 5. We conclude that @entity842 -mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in @entity842 production (as measured by urinary @entity1507 ) in the circulation of older @entity1 . The blunted response to @entity1063 points to a more generalized reduction in vascular reactivity in the elderly.

Impaired XXXX -mediated vasodilatation and total body @entity842 production in healthy old age.

@entity1 :: ('9606', 'Species') :: ['people'] @entity101 :: ('MESH:D006973', 'Disease') :: ['hypertension'] @entity66 :: ('MESH:D004194', 'Disease') :: ['atheromatous disease'] @entity1507 :: ('CHEBI:48107', 'Chemical') :: ['nitrate'] @entity7293 :: ('CHEBI:28229', 'Chemical') :: ['L-NMMA', 'NG-monomethyl-L-arginine'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine'] @entity1063 :: ('MESH:D009638', 'Chemical') :: ['Noradrenaline', 'noradrenaline'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose'] @entity165 :: ('MESH:D002784', 'Chemical') :: ['cholesterol']
@entity842 :: (MESH:D009569,Chemical) :: ['nitric oxide']
