Acute ACE inhibition with enalaprilat or perindoprilat in dogs with heart failure produced similar hemodynamic effects, associated with a 60-80% decrease in angiotensin II and a 4- to 10-fold increase in bradykinin-(1-9).
Does acute ACE inhibition with enalaprilat or perindoprilat alter hemodynamics and circulating levels of angiotensin and bradykinin in dogs with pacing-induced heart failure?
Acute ACE inhibition in a canine model of heart failure improves hemodynamics, which correlates with both a reduction in angiotensin II and an increase in bradykinin-(1-9) levels.
To determine the short-term effects of angiotensin-converting enzyme (ACE) inhibition on hemodynamics and circulating levels of norepinephrine, angiotensin, and bradykinin, responses to enalaprilat and perindoprilat were examined at doses of 0.03, 0.3, and 1 mg/kg in permanently instrumented conscious dogs with pacing-induced heart failure (right ventricular pacing, 240-250 beats/min, 3 weeks). All doses of the two inhibitors produced similar decrease in mean aortic pressure and increase in cardiac output. Neither inhibitor 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 angiotensin II/angiotensin I ratio. There were also a fourfold to 10-fold increase 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) ratio. In addition, the changes in total peripheral resistance induced by the two ACE inhibitors were weakly but significantly correlated with the changes in blood angiotensin II or blood bradykinin-(1-9). Thus whatever the specificity of enalaprilat and perindoprilat, both inhibitors produced similar acute hemodynamic effects in dogs with heart failure, which was associated with marked decrease in circulating angiotensin II level and increase in bradykinin-(1-9) level. This study, which measures for the first time in heart failure the blood bradykinin level after ACE inhibitors, indicates, in concert with angiotensin II reduction, a role for increased bradykinin-(1-9) level in mediating short-term hemodynamic effects of ACE inhibition in this model of heart failure.
Su et al. (Mon,) conducted a other in Heart failure (pacing-induced in dogs). Enalaprilat and perindoprilat was evaluated on Hemodynamics and circulating levels of norepinephrine, angiotensin, and bradykinin. Acute ACE inhibition with enalaprilat or perindoprilat in dogs with heart failure produced similar hemodynamic effects, associated with a 60-80% decrease in angiotensin II and a 4- to 10-fold increase in bradykinin-(1-9).