Bradykinin (B2) independent effect of captopril on the development of pressure overload cardiac hypertrophy.
Besides the reduction of angiotensin II formation, locally increased kinins may play a role in the cardiovascular action of angiotensin converting enzyme (ACE) inhibitors. To characterize the contribution of bradykinin to the effects of ACE inhibition by captopril on the development of pressure overload hypertrophy, sham-operated rats and rats with ascending aortic constriction were treated with captopril (80 mg/kg/day) or captopril and B2 kinin receptor antagonist HOE 140 (0.5 mg/kg/day) for 7 weeks. Left ventricular mass and geometry, hydroxyproline concentration and myosin isozymes (marker of a fetal phenotype) were assessed. Rats with aortic constriction exhibited a marked increase in left ventricular weight and diastolic pressure-volume relationship was shifted to smaller volumes. Signs of congestive heart failure were not apparent. The hydroxyproline concentration remained unaltered. However, the proportion of isomyosin V3 was increased (p < 0.05). Administration of captopril reduced (p < 0.05) systolic blood pressure, body and cardiac weight in all treated rats. The reduction of left ventricular weight was disproportionally higher in pressure overloaded rats, thus the relative left ventricular weight decreased by 15% (p < 0.05). Captopril augmented the isomyosin V1 expression (p < 0.05) in sham operated as well as pressure overloaded rats. The isomyosin V1 percentage was inversely related to the relative left ventricular weight. Two different (p < 0.05) correlation lines were detected for untreated and captopril treated rats. None of captopril associated effects were removed by simultaneously administered B, kinin receptor antagonist HOE 140. Thus, stimulation of bradykinin B2 receptor appears not to mediate the effects of captopril on cardiac growth and contractile proteins during the development of pressure overload hypertrophy.
Turcani
M
M
Institute of Pathophysiology, Medical School, Comenius University, Bratislava, Slovak Republic.
Rupp
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D009218:Myosins / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D013599:Systole / Q000187:drug effects
D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; C065679:icatibant; D002216:Captopril; D009218:Myosins; D006909:Hydroxyproline; D001920:Bradykinin