title: Antioxidant/oxidant status and cardiac function in bradykinin B(1)- and B(2)-receptor null mice.
abstract: Kinin-vasoactive peptides activate two G-protein-coupled receptors (R), B(1)R (inducible) and B(2)R (constitutive). Their complex role in cardiovascular diseases could be related to differential actions on oxidative stress. This study investigated impacts of B(1)R or B(2)R gene deletion in mice on the cardiac function and plasma antioxidant and oxidant status. Echocardiography-Doppler was performed in B(1)R (B(1)R(-/-)) and B(2)R (B(2)R(-/-)) deficient and wild type (WT) adult male mice. No functional alteration was observed in B(2)R(-/-) hearts. B(1)R(-/-) 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 B(1)R(-/-) mice provide a model of moderate systolic dysfunction, whereas B(2)R(-/-) mice displayed a normal cardiac phenotype. Plasma antioxidant capacity (ORAC) was significantly decreased in both B(1)R(-/-) and B(2)R(-/-) mice whereas the vitamin C levels were decreased in B(2)R(-/-) mice only. Plasma ascorbyl free radical was significantly higher in B(1)R(-/-) compared to WT and B(2)R(-/-) mice. Therefore, the oxidative stress index, ascorbyl free radical to vitamin C ratio, was increased in both B(1)R(-/-) and B(2)R(-/-) mice. Hence, B(1)R and B(2)R 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 B(1)R and B(2)R roles in oxidative stress and cardiovascular diseases remain to be investigated.
authors.affiliation: COHIRO Biotechnology, Faculty of Medicine, Dijon, France. sdelemasure@cohiro.fr.
authors.forename: S
authors.initials: S
authors.lastname: Delemasure
authors.forename: N
authors.initials: N
authors.lastname: Blaes
authors.forename: C
authors.initials: C
authors.lastname: Richard
authors.forename: R
authors.initials: R
authors.lastname: Couture
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: P
authors.initials: P
authors.lastname: Dutartre
authors.forename: J-P
authors.initials: JP
authors.lastname: Girolami
authors.forename: J-L
authors.initials: JL
authors.lastname: Connat
authors.forename: L
authors.initials: L
authors.lastname: Rochette
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000097:blood; D018619:Echocardiography, Doppler, Pulsed; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D043783:Receptor, Bradykinin B1 / Q000172:deficiency* / Q000235:genetics; D043782:Receptor, Bradykinin B2 / Q000172:deficiency* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; C000820:semidehydroascorbic acid; D003683:Dehydroascorbic Acid