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

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Abstract

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.

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References

  1. Dzau VJ. Significance of the vascular renin-angiotensin pathway. Hypertension 1986;8:553-559.

    Google Scholar 

  2. Lindpaintner K, Ganten D. The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence. Circ Res 1991;68:905-921.

    Google Scholar 

  3. Hirsch AT, Pinto YM, Schunkert H, Dzau VJ. Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure. Am J Cardiol 1990;66: 22D-32D.

    Google Scholar 

  4. Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ. Tissue specific activation of cardiac angiotensin-converting enzyme in experimental heart failure. Circ Res 1991;69:475-482.

    Google Scholar 

  5. Schelling P, Fischer H, Ganten D. Angiotensin and cell growth: a link to cardiovascular hypertrophy? J Hypertens 1991;9:3-15.

    Google Scholar 

  6. Schiffrin EL, Deng LY, Larochelle P. A prospective trial of effects of converting enzyme inhibitor vs a beta-blocker on structure and function of resistance arteries form mild hypertensive patients. J Hypertens 1994;12(Suppl. 3):S70-S88.

    Google Scholar 

  7. Nakashima Y, Fouad FM, Tarazi RZ. Regression of left ventricular hypertrophy from systemic hypertension by enalapril. Am J Cardiol 1984;53:1044-1049.

    Google Scholar 

  8. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction-results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669-677.

    Google Scholar 

  9. Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study. N Engl J Med 1987;316:1429-1435.

    Google Scholar 

  10. Buikema H, Pinto YM, Rooks G, Grandjean JG, Gilst van WH. The deletion polymorphism of the angiotensin-converting enzyme gene is related to phenotypic differences in human arteries. Eur Heart J 1996;17:787-794.

    Google Scholar 

  11. Buikema H, Pinto YM, Geel van PP, et al. Differential inhibition of plasma versus tissue ACE by utibapril: biochemical and functional evidence for inhibition of vascular ACE activity. J Cardiovasc Pharmacol 1997;29:684-691.

    Google Scholar 

  12. Voors AA, Pinto YM, Buikema H, et al. Dual pathway for angiotensin II formation in human internal mammary arteries. Br J Pharmacol 1998;125:1028-1032.

    Google Scholar 

  13. Long Zhuo J, Froomes P, Casley D, et al. Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease. Circulation 1997;96: 174-182.

    Google Scholar 

  14. Mancini J, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND study. Circulation 1996;94:258-265.

    Google Scholar 

  15. Sedman AJ, Posvar E. Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure. Angiology 1989;40:360-369.

    Google Scholar 

  16. Nussberger J, Waeber G, Waeber B, Bidiville J, Brunner HR. Plasma angiotensin-(1-8) octapeptide measurement to assess acute angiotensin-converting enzyme inhibition with captopril administered parenterally to normal subjects. J Cardiovasc Pharmacol 1988;11:716-721.

    Google Scholar 

  17. Schnaper HW. Comparison of the efficacy and safety of quinapril vs captopril in treatment of moderate to severe hypertension. Angiology 1989;40:389-395.

    Google Scholar 

  18. Okunishi H, Oka Y, Shioto N, Kawanoto T, Song K, Miyazaki M. Marked species-difference in the vascular angiotensin II-forming pathway: Humans versus rodents. Jpn J Pharmacol 1993;62:207-210.

    Google Scholar 

  19. Skidgel RA, Erdos EG. Biochemistry of angiotensin converting enzyme. In: Robertson HS, Nicolls MG, eds. The Renin-Angiotensin System. London: Gower Medical Publishers, 1993.

    Google Scholar 

  20. Gavras I. Bradykinin-mediated effects of ACE-inhibition. Kidney Int 1992;42:1020-1029.

    Google Scholar 

  21. Auch-Schwelk W, Bossaller C, Claus M, Graf M, Fleck E. ACE inhibitors are endothelium dependent vasodilators of coronary arteries during submaximal stimulation with bradykinin. Cardiovasc Res 1993;27:312-317.

    Google Scholar 

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Oosterga, M., Voors, A.A., Buikema, H. et al. Angiotensin II Formation in Human Vasculature after Chronic ACE Inhibition: A Prospective, Randomized, Placebo-Controlled Study. Cardiovasc Drugs Ther 14, 55–60 (2000). https://doi.org/10.1023/A:1007843205311

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