Published Online
on February 17, 2003

A more recent version of this article appeared on March 1, 2003

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Submitted on July 9, 2002
Revised on August 21, 2002

Myocardial Uptake and Biochemical and Hemodynamic Effects of ACE Inhibitors in Humans

Christopher J. Zeitz; Duncan J. Campbell; and John D. Horowitz^*

From the University of Adelaide, Department of Medicine, The Queen Elizabeth Hospital (C.J.Z., J.D.H.), Adelaide, South Australia, and St Vincent's Institute of Medical Research and the University of Melbourne Department of Medicine (D.J.C.), Fitzroy, Victoria, Australia.

^* To whom correspondence should be addressed. E-mail: John.Horowitz{at}adelaide.edu.au.

Abstract--There is little information on the processes affecting selective tissue ACE inhibition and the implications in human subjects. We compared intravenously administered ACE inhibitors, perindoprilat and enalaprilat, for myocardial drug uptake and effects on angiotensin and bradykinin peptides versus hemodynamic effects in 25 patients with stable angina and well-preserved left ventricular systolic function. Myocardial uptake was rapid and more efficient for perindoprilat than for enalaprilat (peak content at 26±3 and 30±4 seconds, 0.58±0.12% and 0.27±0.07% of the administered dose for perindoprilat and enalaprilat, respectively, P=0.04 for difference). Both drugs caused a decrease in angiotensin (Ang) II level, an increase in Ang I level, and reduction in Ang II/Ang I ratio in arterial and coronary sinus blood. Bradykinin (BK)-(1-9) and BK-(1-8) levels increased in arterial blood and BK-(1-8) levels increased in coronary sinus blood after drug administration. Perindoprilat and enalaprilat caused a small decrease in mean arterial pressure (-3±1%, P<0.05; and -4±1%, P<0.01, respectively) and LV+dP/dt (-5.8±1.7%, P<0.01 and -4.2±2.8%, P<0.05, respectively), whereas systemic vascular resistance index was unchanged. Despite relatively cardioselective uptake of perindoprilat, both drugs had similar effects on the cardiac metabolism of angiotensin and bradykinin and on cardiac function. Under resting conditions, both drugs exerted small negative inotropic effects.

Key words: metabolism • hemodynamics • bradykinin • angiotensin • myocardium • enalapril

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