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. 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. 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.
Authors: F Catella-Lawson; B McAdam; B W Morrison; S Kapoor; D Kujubu; L Antes; K C Lasseter; H Quan; B J Gertz; G A FitzGerald Journal: J Pharmacol Exp Ther Date: 1999-05 Impact factor: 4.030
Authors: D S Celermajer; K E Sorensen; D J Spiegelhalter; D Georgakopoulos; J Robinson; J E Deanfield Journal: J Am Coll Cardiol Date: 1994-08 Impact factor: 24.094
Authors: S Taddei; A Virdis; P Mattei; L Ghiadoni; A Gennari; C B Fasolo; I Sudano; A Salvetti Journal: Circulation Date: 1995-04-01 Impact factor: 29.690
Authors: B F McAdam; F Catella-Lawson; I A Mardini; S Kapoor; J A Lawson; G A FitzGerald Journal: Proc Natl Acad Sci U S A Date: 1999-01-05 Impact factor: 11.205
Authors: Daniel Bulut; Sina Liaghat; Christoph Hanefeld; Rouven Koll; Thomas Miebach; Andreas Mügge Journal: J Hypertens Date: 2003-09 Impact factor: 4.844
Authors: Md Sahab Uddin; Md Tanvir Kabir; Md Jakaria; Abdullah Al Mamun; Kamal Niaz; Md Shah Amran; George E Barreto; Ghulam Md Ashraf Journal: Neurotox Res Date: 2019-05-04 Impact factor: 3.911
Authors: Jacqueline K Limberg; Darren P Casey; Joel D Trinity; Wayne T Nicholson; D Walter Wray; Michael E Tschakovsky; Daniel J Green; Ylva Hellsten; Paul J Fadel; Michael J Joyner; Jaume Padilla Journal: Am J Physiol Heart Circ Physiol Date: 2019-12-30 Impact factor: 4.733