Angiotensin II Formation in Human Vasculature after Chronic ACE Inhibition: A Prospective, Randomized, Placebo-Controlled Study

The QUO VADIS (the effects of QUinapril On Vascular Ace and Determinants of ISchemia) study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of long-term angiotensin-converting enzyme (ACE) inhibition on angiotensin II formation in human vasculature. Patients (n < 187) scheduled for coronary artery bypass surgery used study medication 27 ± 1 days before surgery. Segments of internal mammary arteries were exposed to increasing doses (0.1 nM-1 µM) of angiotensin I and II in organ baths. The rate of local angiotensin II formation is a function of the reciprocal of the difference between the pEC₅₀'s of the dose response curves to angiotensin I and II (–log/mol) and of the area between the curves (units). Quinapril (40 mg) and captopril (3×50 mg) similarly and significantly reduced mean blood pressure compared with placebo (p = 0.04). Difference between pEC₅₀'s was 0.90 ± 0.08 in quinapril patients compared with 0.60 ± 0.08 for placebo (p <5 0.01); the area between curves was 91 ± 8 for quinapril patients compared with 67 ± 8 for placebo (p = 0.03). Angiotensin II formation was decreased to a lesser extent with captopril and was not statistically different from placebo (p = 0.3); the difference between pEC₅₀'s was 0.83 ± 0.15; the area between curves was 84 ± 12. This is the first randomized study to demonstrate that long-term oral treatment with an ACE inhibitor reduces vascular angiotensin II formation in humans.