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 d esigned 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 medicati on 27 +/- 1 days before surgery. Segments of internal mammary arteries were exposed to increasing doses (0.1 nM-1 mu M) of angiotensin I and II in org an baths. The rate of local angiotensin II formation is a function of the r eciprocal of the difference between the pEC(50)'s of the dose response curv es to angiotensin I and II (-log/mol) and of the area between the curves (u nits). Quinapril (40 mg) and captopril (3x50 mg) similarly and significantl y reduced mean blood pressure compared with placebo (p = 0.04). Difference between pEC(50)'s was 0.90 +/- 0.08 in quinapril patients compared with 0.6 0 +/- 0.08 for placebo (p < 5 0.01); the area between curves was 91 +/- 8 f or quinapril patients compared with 67 +/- 8 for placebo (p = 0.03). Angiot ensin II formation was decreased to a lesser extent with captopril and was not statistically different from placebo (p = 0.3); the difference between pEC(50)'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 wi th an ACE inhibitor reduces vascular angiotensin II formation in humans.