Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults.
OBJECTIVE
A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both.


METHODS
We tested this hypothesis in 12 younger (age 18-38 years, six women) and 12 older healthy adults (age 55-73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl(-1) forearm tissue min(-1) ) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial N(G) -monomethyl-l arginine acetate (L-NMMA).


RESULTS
Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups.


CONCLUSIONS
In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.
Departments of Anesthesiology, Physiology and Biomedical Engineering, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905.
John H
JH
Eisenach
Leah R
LR
Gullixson
Alexander R
AR
Allen
Susan L
SL
Kost
Wayne T
WT
Nicholson
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine
ageing; forearm blood flow; nitric oxide; prostacyclin; vascular function