Abstract
Purpose
Aging impairs vascular function in women, with the largest detrimental effects occurring during the menopausal transition. Deficiency in the nitric oxide system has been suggested to be responsible for impairment in vascular function with aging, but recent observations suggest that the prostacyclin system, acting in redundancy with the nitric oxide system, may be of importance too. Improvement in vascular function is a hallmark of exercise training and we hypothesize that leg vascular function is improved by exercise training in late postmenopausal women, and that the underlying mechanism is increased endothelial formation of prostacyclin and responsiveness to prostacyclin by the vascular smooth muscle cells.
Method
Femoral-arterial infusion of acetylcholine and epoprostenol was used to assess vascular function and prostacyclin release in ten late postmenopausal women (62 ± 7 years) before and after 10 weeks of high-intensity interval training (floorball conducted as small-sided games).
Result
The training intervention increased fitness level (V̇O2max) by 7 ± 7% and reduced systolic and diastolic blood pressure by 10 ± 10 and 5 ± 6 mmHg, respectively. Leg vascular responsiveness to during acetylcholine and epoprostenol infusion was unchanged with training, whereas the release of prostacyclin during acetylcholine infusion increased by 125%.
Conclusions
In late postmenopausal women, vascular function assessed by femoral-arterial infusion of acetylcholine was not improved after 10 weeks of floorball training, but acetylcholine-induced prostacyclin formation and blood pressure were substantially improved. It is possible that a longer training period could lead to improvements in vascular function and that the observed increase in prostacyclin formation is one of the initial underlying changes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- ERRα:
-
Estrogen related receptor α
- PGI2:
-
Prostacyclin
- NO:
-
Nitric oxide
References
Benjamin EJ, Muntner P, Alonso A et al (2019) Heart disease and stroke statistics—2019 update: a report from the American Heart Association. Circulation. https://doi.org/10.1161/CIR.0000000000000659
Clifford PS, Hellsten Y (2004) Vasodilatory mechanisms in contracting skeletal muscle. J Appl Physiol 97:393–403. https://doi.org/10.1152/japplphysiol.00179.2004
de Sousa CV, Sales MM, Rosa TS et al (2017) The antioxidant effect of exercise: a systematic review and meta-analysis. Sports Med Auckl NZ 47:277–293. https://doi.org/10.1007/s40279-016-0566-1
DeSouza CA, Shapiro LF, Clevenger CM et al (2000) Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation 102:1351–1357. https://doi.org/10.1161/01.CIR.102.12.1351
Eaker ED, Chesebro JH, Sacks FM et al (1993) Cardiovascular disease in women. Circulation 88:1999–2009
Eskurza I, Seals DR, DeSouza CA, Tanaka H (2001) Pharmacologic versus flow-mediated assessments of peripheral vascular endothelial vasodilatory function in humans. Am J Cardiol 88:1067–1069. https://doi.org/10.1016/s0002-9149(01)01997-x
Gliemann L, Hellsten Y (2019) The exercise timing hypothesis: can exercise training compensate for the reduction in blood vessel function after menopause if timed right? J Physiol 16:JP277056. https://doi.org/10.1113/JP277056
Gliemann L, Nyberg M, Hellsten Y (2014) Nitric oxide and reactive oxygen species in limb vascular function: what is the effect of physical activity? Free Radic Res 48:71–83. https://doi.org/10.3109/10715762.2013.835045
Gliemann L, Rytter N, Tamariz-Ellemann A et al (2020) Lifelong physical activity determines vascular function in late postmenopausal women. Med Sci Sports Exerc 52:627–636. https://doi.org/10.1249/MSS.0000000000002180
Gluais P, Lonchampt M, Morrow JD et al (2005) Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br J Pharmacol 146:834–845. https://doi.org/10.1038/sj.bjp.0706390
Gunnarsson TP, Ehlers TS, Fiorenza M et al (2020) Essential hypertension is associated with blunted smooth muscle cell vasodilator responsiveness and is reversed by 10–20-30 training in men. Am J Physiol Physiol. https://doi.org/10.1152/ajpcell.00047.2020
Hellsten Y, Gliemann L (2018) Limb vascular function in women—effects of female sex hormones and physical activity. Transl Sports Med 1:14–24. https://doi.org/10.1002/tsm2.3
Hellsten Y, Jensen L, Thaning P et al (2012) Impaired formation of vasodilators in peripheral tissue in essential hypertension is normalized by exercise training: role of adenosine and prostacyclin. J Hypertens 30:2007–2014
Lind L, Hall J, Johansson K (2002) Evaluation of four different methods to measure endothelium-dependent vasodilation in the human peripheral circulation. Clin Sci Lond Engl 1979 102:561–567
Mendelsohn ME, Karas RH (2005) Molecular and cellular basis of cardiovascular gender differences. Science 308:1583–1587. https://doi.org/10.1126/science.1112062
Moreau KL, Hildreth KL (2014) Vascular aging across the menopause transition in healthy women. Adv Vasc Med 2014:1–12. https://doi.org/10.1155/2014/204390
Moreau KL, Ozemek C (2017) Vascular adaptations to habitual exercise in older adults: time for the sex talk. Exerc Sport Sci Rev 45:116–123. https://doi.org/10.1249/JES.0000000000000104
Moreau KL, Stauffer BL, Kohrt WM, Seals DR (2013) Essential role of estrogen for improvements in vascular endothelial function with endurance exercise in postmenopausal women. J Clin Endocrinol Metab 98:4507–4515. https://doi.org/10.1210/jc.2013-2183
Nielsen G, Wikman JM, Jensen CJ et al (2014) Health promotion: the impact of beliefs of health benefits, social relations and enjoyment on exercise continuation. Scand J Med Sci Sports 24(Suppl 1):66–75. https://doi.org/10.1111/sms.12275
Novella S, Dantas AP, Segarra G et al (2012) Vascular aging in women: is estrogen the fountain of youth? Front Physiol 3:165. https://doi.org/10.3389/fphys.2012.00165
Nyberg M, Egelund J, Mandrup CM et al (2016) Early postmenopausal phase is associated with reduced prostacyclin-induced vasodilation that is reversed by exercise training: the Copenhagen women study. Hypertension 68:1011–1020. https://doi.org/10.1161/HYPERTENSIONAHA.116.07866
Nyberg M, Egelund J, Mandrup CM et al (2017) Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity exercise training are enhanced in the early postmenopausal phase. J Physiol 595:2969–2983. https://doi.org/10.1113/JP273871
Pierce GL, Eskurza I, Walker AE et al (2011) Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults. Clin Sci 120:13–23. https://doi.org/10.1042/CS20100174
Santos-Parker JR, Strahler TR, Vorwald VM et al (2017) Habitual aerobic exercise does not protect against micro- or macrovascular endothelial dysfunction in healthy estrogen-deficient postmenopausal women. J Appl Physiol 122:11–19. https://doi.org/10.1152/japplphysiol.00732.2016
Seals DR, Nagy EE, Moreau KL (2019) Aerobic exercise training and vascular function with ageing in healthy men and women. J Physiol 597:4901–4914. https://doi.org/10.1113/JP277764
Seidelin K, Nyberg M, Piil P et al (2017) Adaptations with intermittent exercise training in post- and premenopausal women. Med Sci Sports Exerc 49:96–105. https://doi.org/10.1249/MSS.0000000000001071
Sobrino A, Oviedo PJ, Novella S et al (2010) Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-alpha. J Mol Endocrinol 44:237–246. https://doi.org/10.1677/JME-09-0112
Stanhewicz AE, Wenner MM, Stachenfeld NS (2018) Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan. Am J Physiol Heart Circ Physiol 315:H1569–H1588. https://doi.org/10.1152/ajpheart.00396.2018
Taddei S, Galetta F, Virdis A et al (2000) Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation 101:2896–2901
Taddei S, Virdis A, Ghiadoni L et al (2006) Endothelium, aging, and hypertension. Curr Hypertens Rep 8:84–89
Thijssen DHJ, de Groot PCE, Smits P, Hopman MTE (2007) Vascular adaptations to 8-week cycling training in older men. Acta Physiol Oxf Engl 190:221–228. https://doi.org/10.1111/j.1748-1716.2007.01685.x
Tingley D, Yamamoto T, Hirose K et al (2014) Mediation: R package for causal mediation analysis. J Stat Softw. https://doi.org/10.18637/jss.v059.i05
Tunstall-Pedoe H, Kuulasmaa K, Amouyel P et al (1994) Myocardial infarction and coronary deaths in the World Health Organization MONICA project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 90:583–612
Vorup J, Pedersen MT, Melcher PS et al (2017) Effect of floorball training on blood lipids, body composition, muscle strength, and functional capacity of elderly men. Scand J Med Sci Sports 27:1489–1499. https://doi.org/10.1111/sms.12739
Zou MH, Ullrich V (1996) Peroxynitrite formed by simultaneous generation of nitric oxide and superoxide selectively inhibits bovine aortic prostacyclin synthase. FEBS Lett 382:101–104
Funding
The study was supported by The Danish Ministry of Culture and Eva and Henry Frænkels Memorial Found.
Author information
Authors and Affiliations
Contributions
Conceived and designed the study: LG, TG. All authors performed the experiment. Interpretation of data: LG, ATE, TG. Drafted the manuscript: LG. Edited, revised and approved the final version of the manuscript: all authors.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Additional information
Communicated by Philip D Chilibeck.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Gliemann, L., Tamariz-Ellemann, A., Baasch-Skytte, T. et al. Increased prostacyclin formation after high-intensity interval training in late postmenopausal women. Eur J Appl Physiol 120, 1711–1720 (2020). https://doi.org/10.1007/s00421-020-04405-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-020-04405-6