Increased bradykinin levels accompany the hemodynamic response to acute inhibition of angiotensin-converting enzyme in dogs with heart failure

To determine the short-term effects of angiotensin-converting enzyme (ACE) inhibition on hemodynamics and circulating levels of norepinephrine, angiot ensin, and bradykinin, responses to enalaprilat and perindoprilat were exam ined at doses of 0.03, 0.3, and 1 mg/kg in permanently instrumented conscio us dogs with pacing-induced heart failure (right ventricular pacing, 240-25 0 beats/min, 3 weeks). All doses of the two inhibitors produced similar dec rease in mean aortic pressure and increase in cardiac output. Neither inhib itor affected plasma norepinephrine level. Both compounds induced a similar 60-80% decrease in blood angiotensin II level, a similar two- to eightfold increase in blood angiotensin I level, and a 80-95% decrease in the angiot ensin II/angiotensin I ratio. There were also a fourfold to 10-fold increas e in blood bradykinin-(1-9) level, a twofold increase in blood bradykinin-( 1-7) level, and a 70-85% decrease in bradykinin-(1-7)/bradykinin-(1-9) rati o. In addition, the changes in total peripheral resistance induced by the t wo ACE inhibitors were weakly but significantly correlated with the changes in blood angiotensin II or blood bradykinin-(1-9). Thus whatever the speci ficity of enalaprilat and perindoprilat, both inhibitors produced similar a cute hemodynamic effects in dogs with heart failure, which was associated w ith marked decrease in circulating angiotensin II level and increase in bra dykinin-(1-9) level. This study, which measures for the first time in heart failure the blood bradykinin level after ACE inhibitors, indicates, in con cert with angiotensin II reduction, a role for increased bradykinin-(1-9) l evel in mediating short-term hemodynamic effects of ACE inhibition in this model of heart failure.