No Association Between ACE I/D Polymorphism and Cardiovascular Hemodynamics During Exercise in Young Women

M. H. Roltsch; M. D. Brown; B. D. Hand; M. C. Kostek; D. A. Phares; A. Huberty; L. W. Douglass; R. E. Ferrell; J. M. Hagberg

doi:10.1055/s-2004-830436

International Journal of Sports Medicine, Table of Contents

Int J Sports Med 2005; 26(8): 638-644
DOI: 10.1055/s-2004-830436

Physiology & Biochemistry

No Association Between ACE I/D Polymorphism and Cardiovascular Hemodynamics During Exercise in Young Women

M. H. Roltsch¹ ^, ² , M. D. Brown¹ , B. D. Hand¹ , M. C. Kostek¹ , D. A. Phares¹ , A. Huberty³ , L. W. Douglass⁴ , R. E. Ferrell⁵ , J. M. Hagberg¹

¹Department of Kinesiology, University of Maryland, College Park, MD, USA
²Howard University Cancer Center, Howard University, Washington, DC, USA
³Department of Entomology, University of Maryland, College Park, MD, USA
⁴Biometrics Program, Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA
⁵Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

Abstract

The ACE I/D polymorphism has been shown to interact with habitual physical activity levels in postmenopausal women to associate with submaximal and with maximal exercise hemodynamics. This investigation was designed to assess the potential relationships between ACE genotype and oxygen consumption (VO₂), cardiac output (Q), stroke volume (SV), heart rate (HR), blood pressure (BP), total peripheral resistance (TPR), and arteriovenous oxygen difference ([a-v]O₂ diff) during submaximal and maximal exercise in young sedentary and endurance-trained women. Seventy-seven 18 - 35-yr-old women underwent a maximal exercise test and a number of cardiac output tests on a treadmill using the acetylene rebreathing technique. ACE genotype was not significantly associated with VO_2max (II 41.4 ± 1.2, ID 39.8 ± 0.9, DD 39.8 ± 1.1 ml/kg/min, p = ns) or maximal HR (II 191 ± 2, ID 191 ± 1, DD 193 ± 2 bpm, p = ns). In addition, systolic and diastolic BP, (a-v)O₂ diff, TPR, SV, and Q during maximal exercise were not significantly associated with ACE genotype. During submaximal exercise, SBP, Q, SV, HR, TPR, and (a-v)O₂ diff were not significantly associated with ACE genotype. However, the association between diastolic BP during submaximal exercise and ACE genotype approached significance (p = 0.08). In addition, there were no statistically significant interactions between ACE genotype and habitual physical activity (PA) levels for any of the submaximal or the maximal exercise hemodynamic variables. We conclude that the ACE I/D polymorphism was not associated, independently or interacting with habitual PA levels, submaximal, or maximal cardiovascular hemodynamics in young women.

Key words

Cardiac output - stoke volume - heart rate - maximal oxygen consumption - angiotensin converting enzyme

Full Text

References

1 Agerholm-Larsen B, Nordestgaard B G, Tybjaerg-Hansen A. ACE gene polymorphism in cardiovascular disease: Meta-analyses of small and large studies in whites. Thromb Vasc Biol. 2000; 20 484-492
2 Alvarez R, Terrados N, Ortolano R, Iglesias-Cubero G, Reguero J R, Batalla A, Cortina A, Fernandez-Garcia B, Rodriguez C, Braga S, Alvarez V, Coto E. Genetic variation in the renin-angiotensin system and athletic performance. Eur J Appl Physiol. 2000; 82 117-120
3 Bouchard C, An P, Rice T, Skinner J S, Wilmore J H, Gagnon J, Perusse L, Leon A S, Rao D C. Familial aggregation of VO_2max response to exercise training: results from the HERITAGE Family Study. J Appl Physiol. 1999; 87 1003-1008
4 Buikema H, Pinto Y, Rooks G, Grandjean J, Schunkert H, van Gilst W. The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries. Eur Heart J. 1996; 17 787-794
5 Butler R, Morris A D, Burchell B, Struthers A D. DD angiotensin-converting enzyme gene polymorphism is associated with endothelial dysfunction in normal humans. Hypertension. 1999; 33 1164-1168
6 Cambien F, Alhenc-Gelas F, Herbeth B, Andre J L, Rakotovao R, Gonzales M F, Allegrini J, Bloch C. Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study. Am J Hum Genet. 1988; 43 774-780
7 Christensen K L, Jespersen L T, Mulvany M J. Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure. J Hypertens. 1989; 7 83-90
8 Erdos E G. The angiotensin I converting enzyme. Fed Proc. 1977; 36 1760-1765
9 Folkow B. Pathophysiology of hypertension: differences between young and elderly. J Hypertens Suppl. 1993; 11 21-24
10 Fouad F M, Tarazi R C, Bravo E L. Cardiac and hemodynamic effects of enalapril. J Hypertens Suppl. 1983; 1 135-142
11 Gayagay G, Yu B, Hambly B, Boston T, Hahn D, Celermajer D S, Trent R J. Elite endurance athletes and the ACE I allele - the role of genes in athletic performance. Hum Genet. 1998; 103 48-50
12 Hagberg J M, Ferrell R E, McCole S D, Wilund K R, Moore G E. VO_2max is associated with ACE genotype in postmenopausal women. J Appl Physiol. 1998; 85 1842-1846
13 Hagberg J M, McCole S D, Brown M D, Ferrell R E, Wilund K R, Huberty A, Douglass L W, Moore G E. ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women. J Appl Physiol. 2002; 92 1083-1088
14 Inserra F, Romano L, Ercole L, de Cavanagh E M, Ferder L. Cardiovascular changes by long-term inhibition of the renin-angiotensin system in aging. Hypertension. 1995; 25 437-442
15 Jackson A S, Pollock M L. Practical assessment of body composition. Physician Sport Medicine. 1985; 13 76-90
16 Jalil J E, Piddo A M, Cordova S, Chamorro G, Braun S, Jalil R, Vega J, Lavandero S, Lastra P. Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population. Am J Hypertens. 1999; 12 697-704
17 Lajemi M, Gautier S, Benetos A. Rigidity of large arteries and cardiovascular risk. Epidemiological aspects and genetic determinants. Pathol Biol (Paris). 1999; 47 614-622
18 Lakatta E. Aging effects on the vasculature in health: risk factors for cardiovascular disease. Am J Geriatr Cardiol. 1994; 3 11-17
19 Lever A F, Lyall F, Morton J J, Folkow B. Angiotensin II, vascular structure and blood pressure. Kidney Int. 1992; 37 (Suppl) 51-55
20 Linz W, Scholkens B A, Ganten D. Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens (A). 1989; 11 1325-1350
21 Linz W, Scholkens B A, Han Y F. Beneficial effects of the converting enzyme inhibitor, ramipril, in ischemic rat hearts. J Cardiovasc Pharmacol. 1986; 8 91-99
22 Linz W, Wiemer G, Scholkens B A. Role of kinins in the pathophysiology of myocardial ischemia. In vitro and in vivo studies. Diabetes. 1996; 45 51-58
23 McCole S D, Brown M D, Moore G E, Zmuda J M, Cwynar J D, Hagberg J M. Cardiovascular hemodynamics with increasing exercise intensities in postmenopausal women. J Appl Physiol. 1999; 87 2334-2340
24 McCole S D, Brown M D, Moore G E, Zmuda J M, Cwynar J D, Hagberg J M. Enhanced cardiovascular hemodynamics in endurance-trained postmenopausal women athletes. Med Sci Sports Exerc. 2000; 32 1073-1079
25 Montgomery H, Clarkson P, Barnard M, Bell J, Brynes A, Dollery C, Hajnal J, Hemingway H, Mercer D, Jarman P, Marshall R, Prasad K, Rayson M, Saeed N, Talmud P, Thomas L, Jubb M, World M, Humphries S. Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training (see comments). Lancet. 1999; 353 541-545
26 Montgomery H E, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman D E, Jubb M, World M, Thomas E L, Brynes A E, Saeed N, Barnard M, Bell J D, Prasad K, Rayson M, Talmud P J, Humphries S E. Human gene for physical performance. Nature. 1998; 393 221-222
27 Morishlta R, Gibbson G, Ellison K, Lee W, Zhang L, Yu H, Kaneda Y. Evidence for direct local effect of angiotensin in vascular hypertrophy: In vivo gene transfer of angiotensin converting enzyme. J Clin Invest. 1994; 94 978-984
28 Myerson S, Hemingway H, Budget R, Martin J, Humphries S, Montgomery H. Human angiotensin I-converting enzyme gene and endurance performance. J Appl Physiol. 1999; 87 1313-1316
29 Nakai K, Itoh C, Miura Y, Hotta K, Musha T, Itoh T, Miyakawa T, Iwasaki R, Hiramori K. Deletion polymorphism of the angiotensin I-converting enzyme gene is associated with serum ACE concentration and increased risk for CAD in the Japanese. Circulation. 1994; 90 2199-2202
30 Rankinen T, Gagnon J, Perusse L, Chagnon Y C, Rice T, Leon A S, Skinner J S, Wilmore J H, Rao D C, Bouchard C. AGT M235 T and ACE ID polymorphisms and exercise blood pressure in the HERITAGE Family Study. Am J Physiol Heart Circ Physiol. 2000; 279 368-374
31 Rankinen T, Perusse L, Gagnon J, Chagnon Y C, Leon A S, Skinner J S, Wilmore J H, Rao D C, Bouchard C. Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study. J Appl Physiol. 2000; 88 1029-1035
32 Rankinen T, Wolfarth B, Simoneau J A, Maier-Lenz D, Rauramaa R, Rivera M A, Boulay M R, Chagnon Y C, Perusse L, Keul J, Bouchard C. No association between the angiotensin-converting enzyme ID polymorphism and elite endurance athlete status. J Appl Physiol. 2000; 88 1571-1575
33 Samani N, Thompson J, O'Toole L, Channer K, Woods K. A meta-analysis of the association of the deletion allele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation. 1996; 94 708-712
34 Schunkert H. Polymorphism of the angiotensin-converting enzyme gene and cardiovascular disease. J Mol Med. 1997; 75 867-875
35 Sonna L A, Sharp M A, Knapik J J, Cullivan M, Angel K C, Patton J F, Lilly C M. Angiotensin-converting enzyme genotype and physical performance during US Army basic training. J Appl Physiol. 2001; 91 1355-1363
36 Stein J H, Congbalay R C, Karsh D L, Osgood R W, Ferris T F. The effect of bradykinin on proximal tubular sodium reabsorption in the dog: evidence for functional nephron heterogeneity. J Clin Invest. 1972; 51 1709-1721
37 Taylor R R, Mamotte C D, Fallon K, van Bockxmeer F M. Elite athletes and the gene for angiotensin-converting enzyme. J Appl Physiol. 1999; 87 1035-1037
38 Thollon C, Kreher P, Charlon V, Rossi A. Hypertrophy induced alteration of action potential and effects of the inhibition of angiotensin converting enzyme by perindopril in infarcted rat hearts. Cardiovasc Res. 1989; 23 224-230
39 Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet. 1992; 51 197-205
40 Triebwasser J, Johnson R, Burpo R, Campbell J, Reardon W, Blomqvist C. Noninvasive determination of cardiac output by a modified acetylene rebreathing procedure utilizing mass spectrometer measurements. Aviation, Space and Environmental Medicine. 1977; 48 203
41 Vanhoutte P M. Endothelium and control of vascular function. Hypertension. 1989; 13 658-667
42 Yoshimura S, Imai K, Hayashi Y, Hashimoto K. Role of renin-angiotensin system in the pathogenesis of spontaneous myocardial fibrosis in Sprague-Dawley rats: effect of long-term administration of captopril. Tohoku J Exp Med. 1989; 157 241-249

Ph.D. M. H. Roltsch

InDyne, Inc

500E Street, SW, Suite 200

Washington, DC 20024

USA

Phone: + 2024799030

Fax: + 20 24 79 05 11

Email: mroltsch@nasaprs.com