Angiotensin II formation in human vasculature after chronic ACE inhibition: a prospective, randomized, placebo-controlled study. QUO VADIS Investigators.
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 microM) 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 x 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 = 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.
Oosterga
M
M
Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Voors
A A
AA
Buikema
H
H
Pinto
Y M
YM
Haber
H E
HE
Ebels
T
T
Morshuis
W J
WJ
Kingma
J H
JH
Crijns
H J
HJ
van Gilst
W H
WH
D000284:Administration, Oral; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects; D016037:Single-Blind Method
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I