Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults

John H. Eisenach, Leah R. Gullixson, Alexander R. Allen, Susan L. Kost, Wayne T. Nicholson

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

CONCLUSION: 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.

AIM: 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.

METHOD: 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.

Original languageEnglish (US)
Pages (from-to)815-823
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume78
Issue number4
DOIs
StatePublished - Oct 1 2014

Keywords

  • ageing
  • forearm blood flow
  • nitric oxide
  • prostacyclin
  • vascular function

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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