Endocrine Abstracts (2001) 2 P45

Exercise-induced, ACE genotype-dependent rise in serum Angiotensin I-Converting Enzyme

DR Woods1, J Saunders2, A Jones2, S Hurel2, Y Jamshidi2, E Hawe2, J Goldstone2, P Gohlke3, S Humphries2 & H Montgomery2


1Department of Medicine, Freeman Hospital, Newcastle Upon Tyne, UK; 2Department of Medicine, University College, London, UK; 3Institute of Pharmacology, University of Kiel, Germany.


Background: The ACE I/D polymorphism of the ACE gene, associated with cardiovascular risk and athletic performance, accounts for half the variation in resting ACE. DD subjects have the greatest, ID intermediate, and II subjects the lowest serum ACE. Exercise stimulates the renin-angiotensin system, producing a rise in angiotensin II. 3 small (n=6-8) lab studies suggest serum ACE does not change with exercise, despite a rise in angiotensin II, whereas 2 other studies have demonstrated an increase in ACE.

Aim: To clarify if the ACE genotype influences any serum ACE response to exercise.

Method: Venous blood was sampled from 17 healthy, male Caucasian subjects after 35 mins rest and immediately after 20 mins of cycle ergometry at 70% Vo2 max. Serum ACE was assayed by a fluorometric method (value used in analysis being the mean of 2 assays from the same time point). Resting, absolute difference and percentage change in ACE were calculated. Local ethical committee approval was obtained.

Results: 7 II, 4 ID and 6 DD subjects (23.8±1.8 years, 176.5±2.7 cm, 73.5±2.4kg, mean±sem) completed the study. Baseline ACE activity (nmol His/Leu/ml/min, mean±sem) was significantly different between the II (25.9±2.5), ID (28.7±2.8) and DD subjects (45.4±3.1), p<0.001 by ANOVA. The whole-group increase in ACE activity with exercise (4.63±0.67) was highly significant (p<0.0005 by paired t-test). II subjects (p=0.0002) and ID subjects (p=0.016) significantly increased ACE but DD subjects did not (p=0.054). The change in ACE over baseline was genotype dependent, increasing 19% in II, and ID subjects and 8.6% in DD (p=0.03 by ANOVA for gene effect, p=0.007 for presence of I allele).

Conclusion: This is the first study to report that, contrary to previous findings, serum ACE activity does increase with exercise, but in an ACE genotype-dependent manner. This probably reflects increased release of membrane bound ACE.

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