Effect of kinin B2 receptor ablation on skeletal muscle development and myostatin gene expression

Bradykinin (BK) is an active peptide that binds to the kinin B2 receptor and induces biological events during the development and adult life. In this study we aimed to investigate the effect of kinin B2 receptor ablation in the postnatal skeletal muscle development and body composition in adult life. For studies of skeletal muscle development, control (C57Bl6 – WT) and B2 receptor knockout mice (B2-/-) were sacrificed at 15, 30 and 90 days after birth, the gastrocnemius skeletal muscle was weighed and myostatin gene expression evaluated by real time PCR. For energy balance determination, data from control and B2-/- at 90 and 120 days were collected by calorimetric method. Body composition at 120 days was determined by chloroform–methanol (total body fat) and Lowry-modified method (total body protein). The results show that B2-/- have significantly increased total body weight at 15, 30 and 90 days of life, when compared to WT. The weight of the gastrocnemius skeletal muscle was also significantly increased at 30 and 90 days of life. Body composition analyses revealed that B2-/- mice exhibit more total corporal protein and less total corporal fat. Energy balance revealed that B2-/- have increased metabolizable energy intake and energy expenditure when compared to control mice, resulting in a lower energy gain. Interestingly, myostatin mRNA expression was significantly decreased in 15 and 30 days old B2-/- mice and after icatibant treatment of WT adult mice for 5 days. In conclusion, together our results show that kinin B2 receptor deletion increases lean mass, reduces fat mass and improves metabolism efficiency in mice. The mechanism involved in this phenotype could be related to the reduction of myostatin gene expression during postnatal life.