Proceedings of The Physiological Society

Kings College London (2005) J Physiol 565P, C174


Cardiac power output and its relationship with bradykinin receptor gene (BK2)

Hodges, LD ; Dhamrait, S ; Montgomery, H ; Brodie, DA ;

1. Research Centre for Health Studies, Buckinghamshire Chilterns University College, Chalfont St Giles, United Kingdom. 2. Rayne Institute, University College London, London, United Kingdom.

The central function of the heart is contraction and like all muscles the myocardium must make use of metabolically available energy to produce mechanical work. Cardiac power output is equivalent to the rate at which the heart imparts hydraulic energy into the arterial system to maintain the circulation of blood. All individuals have the BK2 receptor and BKBR2 gene. The expression of the absence (-9) rather than the presence (+9) of a 9 base pair repeat in the gene encoding bradykinin 2 receptor (B2BKR) is associated with greater gene expression and lower cardiac trophic responses to exercise. The purpose of this study was to explore the relationship of the absence or presence of a 9 base pair B2BKR with cardiac power output. Fifty seven subjects underwent maximal cardiopulmonary exercise testing. Subjects provided a mouthwash sample using a 10 ml of 0.9% sodium chloride solution. The DNA was extracted from the cheek cells contained in the sample. B2R genotype was ascertained using forward 5’TCTGGCTTCTGGGCTCCGAG-3’ and reverse 5’AGCGGGCATGGGACTTCAGT-3’ primers. Genotype distributions in the cohort in which homozygotes were drawn were consistent with Hardy-Weinburg equilibrium. Analysis compared individuals who had the +9/+9 (n=12) expression vs. -9/-9 (n=14). Cardiac power output was significantly higher amongst those of +9/+9 genotype than amongst -9 homozygotes (5.19 ± 1.44 W vs. 4.25 ± 0.98 W, (p<0.025). However, there was a non significant difference (p>0.05) in between groups (33.2 ± 12.9 and 29.7 ± 6.7, respectively). As a component of renin-angiotensin systems (RAS), angiotensin converting enzyme (ACE) degrade kinins, lessening their action upon the BK2 receptor. A polymorphic variant of the ACE gene associated with high ACE activity has been associated with improvements in skeletal muscle strength with training, and with ‘power’ related sports. Our data here suggest that these effects may in part be mediated through alterations in kinin activity at the BK2 receptor. They also extend to previous observations to implicate RAS in regulating cardiac (as well as skeletal) muscle function. These novel data suggest a role for myocardial RAS in regulating myocardial energetics and contractile performance. They may have implications for the rational design of newer therapeutic targets for the treatment of myocardial contractile dysfunction and clinical heart failure.

Where applicable, experiments conform with Society ethical requirements