The aim of this study was to determine the possible influence of bradykinin type 2 receptor 9 base pair polymorphism on triceps brachii muscles hypertrophy as a result of six weeks of self-perceived maximal elbow extensors strength training. Since muscle adaptation is in part influenced by heritability, we wanted to investigate the possible influence of bradykinin type 2 receptor gene variants on skeletal muscle adaptation capacity in young adults.
The volume of upper arms elbow extensors increased significantly, by 5.4 ± 3.4%, as a result of a 6-week strength training of our participants. These data are in line with other researchers, since skeletal muscle hypertrophy is a part of muscle adaptation to increased physical activity levels. Different resistance training protocols have been shown to present a variety of exercise demands resulting in adaptations which are specific to the exercise program used [1–3]. Andersen et al. found that m.quadriceps femoris CSA at mid-femur increased by 10% after 3 months resistance training . Abe et al. found relative increases in upper (12% - 21%) and lower (7% - 9%) body muscle thickness in men and 10% - 31% and 7% - 8% in women, respectively . This was after 12 weeks of resistance training, three times per week (six dynamic resistance exercises to fatigue using 8–12 1-repetition maximum – 1RM) in untrained participants .
Skeletal muscle adaptation capacity depends on numerous factors, and the genetic predisposition is certainly one of them. There are number of reports in literature regarding influences of different genes and their polymorphism on skeletal muscle morphological and functional adaptation. In our study, we used MRI to evaluate muscle hypertrophy response to training stimulus, which was maximal according to participants’ personal perception, and investigated if there was an influence of bradykinin type 2 receptor variants on the extent of hypertrophy and strength gains.
We found that the presence of two −9 alleles of the B2BRK leads to significantly higher skeletal muscle hypertrophy after a short-term strength training, compared to the presence of one or two +9 alleles. Montgomery’s group reported that heart muscle hypertrophy is more extensive in individuals with +9/+9 genotype variant, when completing a 10-week physical training protocol . They showed that genotypes that lead to lower bradykinin type 2 receptor concentrations (B2BRK +9/+9) correlate with greater cardiac growth response to increased physical activity. Our data suggest that skeletal muscle responds differently from cardiomyocytes to the increased load. Although pre-training triceps brachii muscle volume and average strength did not appear to be influenced by the bradykinin 9-bp polymorphism, triceps brachii muscle volume increased significantly more in individuals with −9/-9 genotype after 6 weeks of targeted training.
We discovered a significant change in muscle functional properties as a result of strength training. Maximal muscle strength increased by 19.9%, endurance by 48.4%, and fatigue rate decreased by 73.8%. However, bradykinin polymorphism did not correlate with the changes in triceps brachii muscle strength, endurance and fatigue, as a result of a 6-week training. There are only a few reports in the literature on the relationship between polymorphism in the bradykinin type 2 receptor and the functional capacity of skeletal muscles. Williams et al. reported that common 9-bp variation in the B2BRK is associated with efficiency of skeletal muscle contraction (delta efficiency) in both athletes and non-athletes . On the other hand, Hopkinson and associates reported that the genotype with reduced B2BRK expression (+9) is associated with quadriceps strength in chronic obstructive pulmonary diseases .
A possible explanation of our results concerning muscle strength, which are not in line with some other researchers, may be found in the fact that there is a variety of functional muscle properties that can be assessed as a result of specific adaptation to training, and we followed only some of them. It is known that muscle strength is not completely dependent on muscle size, and there are a number of factors that influence strength, endurance, or fatigue, and their change after training, especially in the first 4–6 weeks of programmed physical activity.
Higher transcriptional activity and higher mRNA levels have been associated with the B2BRK −9 allele. Previous work showed that bradykinin could increase glucose uptake in the skeletal muscle during exercise [9, 27]. Activation of bradykinin type 2 receptor could also result in an increased concentration of inositol triphosphate, which gives rise to increased calcium concentration within the cell [28, 29]. Bradykinin has also been shown to induce the production of nitric oxide in the skeletal muscle , which can reduce oxygen consumption in skeletal muscle mitochondria . It can be expected that the higher number of bradykinin type 2 receptors could lead to increased stimulation of skeletal muscle cells when exposed to training stimulus. It is all mediated throughout the increased substrate intake and therefore throughout the increased energy production, which altogether stimulates cell activity and promotes hypertrophic stimulation mechanisms.
Our results suggest that higher bradykinin receptor levels present in individual homozygous for −9 allele of the B2BRK gene may be advantageous in the adaptation of the skeletal muscle to the demands of the training. Ability to gain muscle is especially important in later decades of life, when loss of muscle bulk correlates with poorer quality of life and higher mortality . Identifying gene polymorphisms that influence muscle responsiveness to training could help identify those with higher probability of muscle loss, as well as aid in designing more tailored approaches to training. This finding could be relevant, not only in predicting individual muscle adaptation capacity to training or sarcopenia related to aging and inactivity, but also in determining new therapeutic strategies targeting genetic control of muscle function, especially for neuromuscular disorders that are characterized by progressive adverse changes in muscle quality, mass, strength and force production (e.g., muscular dystrophy, multiple sclerosis, Parkinson’s disease).
Certain limitations need to be considered in the present study. The number of participants was small, especially in a +9/+9 genotype group (only five), and therefore we presented our data set divided into two groups only – one without, and the second with the presence of one or both +9 allele. The reason for this was the fact that the presence of both −9 alleles leads to higher expression of bradykinin receptors, compared to other two genotype combinations. The exercise used in the training could partially engage some other muscles in this area (etc. deltoideus and pectoralis). However, the specific position which the participant had taken (upright seated position, with elbows close to the trunk) and the fact that every session was closely monitored by the investigator, allow us to assume that triceps stimulation was equal during the training process, and that the participation of other muscles was not significant. The aim was not to trace a single trait, its’ distribution in population, nor its’ association with some functional or morphological properties of skeletal muscles. We wanted to explore the possible influence of B2BRK polymorphism on skeletal muscle adaptation capacity after a programmed physical activity protocol, and these changes were followed in the same participant using precise measurements. Also, by applying the identical training and testing procedures in all participants, we additionally diminished the possibility that strength values or their increase were overestimated in some volunteers.