Antioxidant/Oxidant Status and Cardiac Function in Bradykinin B1- and B2-Receptor Null Mice

Abstract

Kinin-vasoactive peptides activate two G-protein-coupled receptors (R), B1R (inducible) and B2R (constitutive). Their complex role in cardiovascular diseases could be related to differential actions on oxidative stress. This study investigated impacts of B1R or B2R gene deletion in mice on the cardiac function and plasma antioxidant and oxidant status. Echocardiography-Doppler was performed in B1R (B1R-/-) and B2R (B2R-/-) deficient and wild type (WT) adult male mice. No functional alteration was observed in B2R-/- hearts. B1R-/- mice had significantly lowered fractional shortening and increased isovolumetric contraction time. The diastolic E and A waves velocity ratio was similar in all mice groups. Thus B1R-/- mice provide a model of moderate systolic dysfunction, whereas B2R-/- mice displayed a normal cardiac phenotype. Plasma antioxidant capacity (ORAC) was significantly decreased in both B1R-/- and B2R-/- mice whereas the vitamin C levels were decreased in B2R-/- mice only. Plasma ascorbyl free radical was significantly higher in B1R-/- compared to WT and B2R-/- mice. Therefore, the oxidative stress index, ascorbyl free radical to vitamin C ratio, was increased in both B1R-/- and B2R-/- mice. Hence, B1R and B2R deficiency are associated with increased oxidative stress, but there is a differential imbalance between free radical production and antioxidant defense. The interrelationship between the differential B1R and B2R roles in oxidative stress and cardiovascular diseases remain to be investigated.