Effect of angiotensin-converting enzyme inhibition on cardiovascular adaptation to exercise training

Abstract

Angiotensin-converting enzyme (ACE) activity may be one determinant of adaptability to exercise training, but well-controlled studies in humans without confounding conditions are lacking. Thus, the purpose of the present study was to investigate whether ACE inhibition affects cardiovascular adaptations to exercise training in healthy humans. Healthy participants of both genders (40 ± 7 years) completed a randomized, double-blind, placebo-controlled trial. Eight weeks of exercise training combined with placebo (PLA, n = 25) or ACE inhibitor (ACEi, n = 23) treatment was carried out. Before and after the intervention, cardiovascular characteristics were investigated. Mean arterial blood pressure was reduced (p < 0.001) by -5.5 [-8.4; -2.6] mmHg in ACE_i , whereas the 0.7 [-2.0; 3.5] mmHg fluctuation in PLA was non-significant. Maximal oxygen uptake increased (p < 0.001) irrespective of ACE inhibitor treatment by 13 [8; 17] % in ACE_i and 13 [9; 17] % in PLA. In addition, skeletal muscle endurance increased (p < 0.001) to a similar extent in both groups, with magnitudes of 82 [55; 113] % in ACE_i and 74 [48; 105] % in PLA. In contrast, left atrial volume decreased (p < 0.05) by -9 [-16; -2] % in ACE_i , but increased (p < 0.01) by 14 [5; 23] % in PLA. Total hemoglobin mass was reduced (p < 0.01) by -3 [-6; -1] % in ACE_i , while a non-significant numeric increase of 2 [-0.4; 4] % existed in PLA. The lean mass remained constant in ACE_i but increased (p < 0.001) by 3 [2; 4] % in PLA. In healthy middle-aged adults, 8 weeks of high-intensity exercise training increases maximal oxygen uptake and skeletal muscle endurance irrespective of ACE inhibitor treatment. However, ACE inhibitor treatment counteracts exercise training-induced increases in lean mass and left atrial volume. ACE inhibitor treatment compromises total hemoglobin mass.

Keywords: angiotensin-converting enzyme inhibitors; cardio-vascular health; exercise; hypertension.

FIGURE 1

Consort diagram. Stratified randomization by gender and angiotensin‐converting enzyme genotype (D/D, I/D, and I/I) was applied to allocate the study participants to angiotensin‐converting enzyme inhibitor (ACEi) or placebo treatment.

FIGURE 2

Exercise capacity adaptations. Values are presented as means (with 95% confidence intervals) from a linear mixed‐model with time, treatment, and time × treatment as explanatory variables. The figure shows maximal oxygen uptake (a), skeletal muscle endurance (b), and rowing performance (c) measured pre‐and post‐intervention in participants treated with an angiotensin‐converting enzyme inhibitor (ACE_i ) or placebo. If a significant effect of time × treatment or time existed, the result of the post hoc analysis is indicated by *p < 0.05, **p < 0.001 compared with pre‐intervention.

FIGURE 3

Treatment efficiency. Values are presented as means (with 95% confidence intervals) from a linear mixed‐model with time, treatment, and time × treatment as explanatory variables. The figure shows mean arterial blood pressure measured at home during the first 2 weeks of the intervention (a) and mean arterial blood pressure measured in a clinical setting pre‐and post‐intervention (b) in participants treated with an angiotensin‐converting enzyme inhibitor (ACE_i ) or placebo. If a significant effect of time × treatment or time existed, the result of the post hoc analysis is indicated by **p < 0.001 compared with pre‐intervention, and ^† p < 0.05 compared with placebo.

FIGURE 4

Hematological adaptations. Values are presented as means (with 95% confidence intervals) from a linear mixed‐model with time, treatment, and time × treatment as explanatory variables. The figure shows total blood volume (a), plasma volume (b), hemoglobin mass (c), and red cell volume (d) measured pre‐and post‐intervention in participants treated with an angiotensin‐converting enzyme inhibitor (ACEi) or placebo. If a significant effect of time × treatment or time existed, the result of the post hoc analysis is indicated by *p < 0.05 compared with pre‐intervention.

FIGURE 5

Body composition adaptations. Values are presented as means (with 95% confidence intervals) from a linear mixed‐model with time, treatment, and time × treatment as explanatory variables. The figure shows lean body mass (a), body fat mass (b), and body fat percentage (c) measured pre‐and post‐intervention in participants treated with an angiotensin‐converting enzyme inhibitor (ACE_i ) or placebo. If a significant effect of time × treatment or time existed, the result of the post hoc analysis is indicated by *p < 0.05, **p < 0.001 compared with pre‐intervention.