Aging is Associated with Reduced Prostacyclin-mediated Dilation in the Human Forearm

Overview

Journal Hypertension

Date 2009 May 6

PMID 19414649

Citations 51

Authors

Wayne T Nicholson

Brianna Vaa

Christiane Hesse

John H Eisenach

Michael J Joyner

Affiliations

Soon will be listed here.

Abstract

Aging is associated with reduced endothelial function. There is indirect evidence for reduced prostacyclin (PGI(2))-mediated vasodilation with aging, but it is unknown whether this is because of reduced dilation to PGI(2) or altered production. In addition, the contribution of endothelial NO to PGI(2)-mediated dilation is unknown. Using plethysmography to determine forearm blood flow, we studied the effect of PGI(2) in 10 older (61 to 73 years) and 10 younger (19 to 45 years) subjects using 3 escalating intra-arterial doses of PGI(2) (epoprostenol). PGI(2) was also administered after NO synthase inhibition with N(G)-monomethyl-l-arginine acetate. The percent of change in forearm vascular conductance (mean+/-SEM) from baseline after PGI(2) was significantly lower (P=0.002) in the aging individuals (52+/-11%, 164+/-23%, and 221+/-27% versus 115+/-20%, 249+/-19%, and 370+/-35%). In addition, the group-by-dose interaction was also significant (P=0.018). After NO synthase inhibition, the dose-response curve to PGI(2) was blunted in the young subjects but unchanged in the older subjects; the difference between the groups was no longer significant. Our data suggest that the reduced dilator effects of PGI(2) in older individuals are attributable to a reduction in the contribution of endothelial-derived NO versus alterations in the direct effects of PGI(2) on vascular smooth muscle.

Citing Articles

Understanding brain function in vascular cognitive impairment and dementia with EEG and MEG: A systematic review.

Torres-Simon L, Doval S, Nebreda A, Llinas S, Marsh E, Maestu F Neuroimage Clin. 2022; 35:103040.

PMID: 35653914 PMC: 9163840. DOI: 10.1016/j.nicl.2022.103040.

Common Shared Pathogenic Aspects of Small Vessels in Heart and Brain Disease.

Moretti R, Janjusevic M, Fluca A, Saro R, Gagno G, Pierri A Biomedicines. 2022; 10(5).

PMID: 35625746 PMC: 9138783. DOI: 10.3390/biomedicines10051009.

Small Vessel Disease: Ancient Description, Novel Biomarkers.

Moretti R, Caruso P Int J Mol Sci. 2022; 23(7).

PMID: 35408867 PMC: 8998274. DOI: 10.3390/ijms23073508.

Impact of age and cyclooxygenase inhibition on the hemodynamic response to acute cognitive challenges.

Pearson A, Miller K, Corkery A, Eisenmann N, Howery A, Carl A Am J Physiol Regul Integr Comp Physiol. 2021; 321(2):R208-R219.

PMID: 34161746 PMC: 8409912. DOI: 10.1152/ajpregu.00048.2021.

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health.

Barnes J, Pearson A, Corkery A, Eisenmann N, Miller K J Int Neuropsychol Soc. 2021; 27(8):761-775.

PMID: 33952365 PMC: 8496967. DOI: 10.1017/S1355617721000394.

References

Engelke K, Halliwill J, Proctor D, Dietz N, Joyner M . Contribution of nitric oxide and prostaglandins to reactive hyperemia in human forearm. J Appl Physiol (1985). 1996; 81(4):1807-14. DOI: 10.1152/jappl.1996.81.4.1807. View

Dietz N, Rivera J, Eggener S, Fix R, Warner D, Joyner M . Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans. J Physiol. 1994; 480 ( Pt 2):361-8. PMC: 1155852. DOI: 10.1113/jphysiol.1994.sp020366. View

Singh N, Prasad S, Singer D, MacAllister R . Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm. Clin Sci (Lond). 2002; 102(5):595-600. View

FitzGerald G . Coxibs and cardiovascular disease. N Engl J Med. 2004; 351(17):1709-11. DOI: 10.1056/NEJMp048288. View

Joyner M, Dietz N, SHEPHERD J . From Belfast to Mayo and beyond: the use and future of plethysmography to study blood flow in human limbs. J Appl Physiol (1985). 2001; 91(6):2431-41. DOI: 10.1152/jappl.2001.91.6.2431. View

Matz R, Andriantsitohaina R . Age-related endothelial dysfunction : potential implications for pharmacotherapy. Drugs Aging. 2003; 20(7):527-50. DOI: 10.2165/00002512-200320070-00005. View

DeSouza C, Clevenger C, Greiner J, Smith D, Hoetzer G, Shapiro L . Evidence for agonist-specific endothelial vasodilator dysfunction with ageing in healthy humans. J Physiol. 2002; 542(Pt 1):255-62. PMC: 2290401. DOI: 10.1113/jphysiol.2002.019166. View

Kamper A, Paul L, Blauw G . Prostaglandins are involved in acetylcholine- and 5-hydroxytryptamine-induced, nitric oxide-mediated vasodilatation in human forearm. J Cardiovasc Pharmacol. 2002; 40(6):922-9. DOI: 10.1097/00005344-200212000-00014. View

Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A . Age-related reduction of NO availability and oxidative stress in humans. Hypertension. 2001; 38(2):274-9. DOI: 10.1161/01.hyp.38.2.274. View

10.

Torgrimson B, Meendering J, Kaplan P, Minson C . Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol. Am J Physiol Heart Circ Physiol. 2007; 292(6):H2874-80. DOI: 10.1152/ajpheart.00762.2006. View

11.

Narumiya S, FitzGerald G . Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest. 2001; 108(1):25-30. PMC: 209349. DOI: 10.1172/JCI13455. View

12.

Tang E, Vanhoutte P . Gene expression changes of prostanoid synthases in endothelial cells and prostanoid receptors in vascular smooth muscle cells caused by aging and hypertension. Physiol Genomics. 2007; 32(3):409-18. DOI: 10.1152/physiolgenomics.00136.2007. View

13.

Schrage W, Dietz N, Eisenach J, Joyner M . Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle. J Appl Physiol (1985). 2004; 98(4):1251-7. DOI: 10.1152/japplphysiol.00966.2004. View

14.

Schrage W, Eisenach J, Joyner M . Ageing reduces nitric-oxide- and prostaglandin-mediated vasodilatation in exercising humans. J Physiol. 2006; 579(Pt 1):227-36. PMC: 2075375. DOI: 10.1113/jphysiol.2006.124313. View

15.

Tao J, Jin Y, Yang Z, Wang L, Gao X, Lui L . Reduced arterial elasticity is associated with endothelial dysfunction in persons of advancing age: comparative study of noninvasive pulse wave analysis and laser Doppler blood flow measurement. Am J Hypertens. 2004; 17(8):654-9. DOI: 10.1016/j.amjhyper.2004.03.678. View

16.

Yildiz O . Vascular smooth muscle and endothelial functions in aging. Ann N Y Acad Sci. 2007; 1100:353-60. DOI: 10.1196/annals.1395.038. View

17.

Solomon D, Schneeweiss S, Glynn R, Kiyota Y, Levin R, Mogun H . Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation. 2004; 109(17):2068-73. DOI: 10.1161/01.CIR.0000127578.21885.3E. View

18.

Celermajer D, Sorensen K, Spiegelhalter D, Georgakopoulos D, Robinson J, Deanfield J . Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994; 24(2):471-6. DOI: 10.1016/0735-1097(94)90305-0. View

19.

Solomon S, Wittes J, Finn P, Fowler R, Viner J, Bertagnolli M . Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation. 2008; 117(16):2104-13. PMC: 2965408. DOI: 10.1161/CIRCULATIONAHA.108.764530. View

20.

Eisenach J, Clark E, Charkoudian N, Dinenno F, Atkinson J, Fealey R . Effects of chronic sympathectomy on vascular function in the human forearm. J Appl Physiol (1985). 2002; 92(5):2019-25. DOI: 10.1152/japplphysiol.01025.2001. View