The phenotype based on the insertion/deletion (I/D) polymorphism of the human angiotensin converting enzyme (ACE) gene has been associated with individual training response. Briefly, intervention studies have demonstrated an 11-fold greater training-induced improvement in muscular endurance for ACE I/I homozygotes compared to ACE D/D homozygotes. Importantly, the ACE I/D polymorphism causes large inter-individual differences in serum ACE activity. Because the ACE D/D genotype is characterized by high plasma ACE activity and potentially blunted endurance exercise training response, it appears likely that ACE inhibitors (ACEi) have the potential to improve the outcome of exercise training for ACE D/D homozygotes. Thus, in the present study the investigators apply a randomized double-blind placebo-controlled longitudinal design to investigate whether pharmacological inhibition of ACE activity can amplify the exercise training response in healthy humans carrying either the ACE D/D or ACE I/I genotype. The study hypothesis is that inhibition of ACE activity in healthy humans with the ACE D/D genotype will amplify the health beneficial effects of exercise training while this is not the case in ACE I/I homozygotes.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
52
Participants will be assigned to daily administration of ACE inhibitors (Initially 5 mg Corodil® 'Enalapril' daily followed by up to 20 mg daily dependent on the blood pressure response) combined with an 8-week training period.
Participants will be assigned to daily administration of placebo (5-20 mg CaCO3) combined with an 8-week training period.
Department of Nutrition, Exercise and Sports
Copenhagen, Denmark
Maximal systemic oxygen uptake
Training-induced changes in maximal systemic oxygen uptake (L/min) is evaluated with an incremental maximal cycle protocol on a cycle ergometer
Time frame: 20 minutes
Skeletal muscle endurance
Training-induced changes in muscle endurance evaluated as changes in duration (sec) of a repetitive elbow-flexion exercise
Time frame: 5 minutes
Blood volume
Training-induced changes in total blood volume (mL) is measured using the Carbon-monoxide rebreathing method.
Time frame: 20 minutes
Endurance performance
Training-induced changes in endurance performance is determined by a 2000 meter time trial on an indoor rowing ergometer
Time frame: 15 minutes
Skeletal muscle oxidative capacity
Training-induced changes in muscle oxidative capacity is evaluated as maximal citrate synthase and 3- hydroxy-acetylCoa-dehydrogenase activity (µmol/g/min)
Time frame: 60 minutes
Mitochondrial biogenesis
Expression of complex I-V will be analyzed in order to evaluate if the applied training induced mitochondrial biogenesis.
Time frame: 60 minutes
Mean arterial pressure (MAP)
Training-induced changes in resting MAP (mmHg) will be estimated using this formula: MAP = diastolic pressure + 1/3 (systolic pressure - diastolic pressure)
Time frame: 10 minutes
Steady-state systemic oxygen uptake
Training-induced changes in steady-state systemic oxygen uptake (mL/min) is determined by indirect calorimetry during a submaximal cycle protocol on a cycle ergometer
Time frame: 10 minutes
Muscle strength
Training-induced changes in muscle strength (kg) is measured using a handgrip dynamometer
Time frame: 1 minute
Fat mass
Training-induced changes in fat mass (kg) is determined by dual-energy x-ray absorptiometry (DXA)-scan
Time frame: 20 minutes
Fat free mass
Training-induced changes in fat free mass (kg) is determined by DXA-scan
Time frame: 20 minutes
Body fat percentage
Training-induced changes in body fat percentage (%) is determined by DXA-scan
Time frame: 20 minutes
Left ventricular (LV) mass
Training-induced changes in LV mass (g) is determined by cardiac magnetic resonance imaging (cMRI)
Time frame: 45 minutes
LV end-diastolic volume
Training-induced changes in LV end-diastolic volume (mL) is determined by cMRI
Time frame: 45 minutes
LV mean wall thickness
Training-induced changes in LV mean wall thickness (cm) is determined by cMRI
Time frame: 45 minutes
LV stroke volume
Training-induced changes in LV stroke volume (mL) is determined by cMRI
Time frame: 45 minutes
LV ejection fraction
LV stroke volume (mL) and LV end-diastolic volume (mL) will be used to measure training-induced changes in LV ejection fraction (%)
Time frame: 45 minutes
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