Effects of aging and atherosclerosis on endothelial and vascular smooth muscle function in humans.
BACKGROUND
Nitric oxide is an endothelium dependent dilator, which may protect against atherosclerosis. Several studies have shown a decrease in nitric oxide activity with aging, however none have assessed aging and atherosclerosis separately. We tested the hypothesis that aging blunts both basal and receptor-mediated endothelial nitric oxide release in humans.


METHODS
We examined whether forearm blood flow responses to intra-arterial acetylcholine, and nitroprusside, were altered with aging, with and without co-infusion of an inhibitor of nitric oxide synthase (N(G)-mono-methyl-L-arginine) in three groups of human subjects; a group with clinical atherosclerotic vascular disease (n = 31, 21 M), otherwise healthy elderly (n = 17, 13 M), and healthy young controls (n = 15, 8 M).


RESULTS
There was no difference in basal flows between the three groups. There was also no difference in the dilatation to either acetylcholine or nitroprusside responses between the AVD and the healthy elderly group; however, aging significantly decreased acetylcholine or nitroprusside responses when compared to the young controls (p < 0.02). Furthermore, the ratio between acetylcholine and nitroprusside, a marker of endothelial NO synthase activity, was significantly greater in the young volunteers (0.816 +/- 0.094% vs. 0.892 +/- 0.146 % vs. 1.389 +/- 0.2%, in atherosclerotic vascular disease, healthy elderly group, and young controls respectively).


CONCLUSIONS
Forearm blood flow responses to endothelium dependent and independent stimuli are blunted with aging, independent of the presence of atherosclerotic disease. Moreover, the normal aging process may induce significant global vascular dysfunction (involving the endothelium and the vascular smooth muscle); to as great a degree as clinically manifest atherosclerosis.
Al-Shaer
Moutasim H
MH
University of Iowa, Internal Medicine, Bettendorf, 52242, USA.
Choueiri
Nabil E
NE
Correia
Marcelo L G
ML
Sinkey
Christine A
CA
Barenz
Therese A
TA
Haynes
William G
WG
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine