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Effect of Long-Term Angiotensin II Type I Receptor Antagonism on Peripheral and Coronary Vasomotion

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Abstract

Angiotensin II, via AT1 receptors plays a key role in endothelial dysfunction and therefore, in atherogenesis. In order to assess whether long-term blockade of these receptors improve peripheral and coronary endothelial function, 13 patients were treated by candesartan cilexetil (AT2B, 16 mg/d in 10 patients and 8 mg in 3). Flow-mediated dilation (FMD, measured with ultra-sound technique) in the brachial artery and cold pressor testing (CPT)-induced changes in myocardial blood flow (MBF, measured with positron emission tomography) were assessed before and after a 6 month treatment period. AT2B did not alter FMD: 5.0 ± 1.2% vs. 6.4 ± 0.9% after treatment. MBF increased significantly during CPT before and after AT2B. Although AT2B did not significantly modify heart rate and blood pressure, MBF normalized to the rate pressure product (MBF/RPP × 10000) was significantly higher and this change remained significant during CPT: it increased from 0.94 ± 0.05 ml/g/min to 1.14 ± 0.09 ml/g/min after AT2B (P < .05) and did not decrease during CPT (1.12 ± 0.08 ml/g/min). Moreover, these AT2B-induced changes in normalized MBF were significantly correlated with the changes in FMD (r = 0.66, P < 0.05).

Thus, long-term AT2B improves coronary vasomotion. Although no significant alteration in peripheral conduit endothelial function has been observed, treatment-induced FMD changes seem to be a predictor of coronary circulation improvement.

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References

  1. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 1996;94:258–265.

    Google Scholar 

  2. Anderson TJ, Elstein E, Haber H, Charbonneau F. Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study). J Am Coll Cardiol 2000;35:60–66.

    Google Scholar 

  3. Schuh JR, Blehm DJ, Frierdich GE, McMahon EG, Blaine EH. Differential effects of renin-angiotensin system blockadeon atherogenesis in cholesterol-fed rabbits. J Clin Invest 1993;91:1453–1458.

    Google Scholar 

  4. Berkenboom G, Langer I, Carpentier Y, Grosfils K, Fontaine J. Ramipril prevents endothelial dysfunction induced by oxidized low-density lipoproteins: A bradykinin-dependent mechanism. Hypertension 1997;30:371–376.

    Google Scholar 

  5. Rajagopalan S, Kurz S, Munzel T, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916–1923.

    Google Scholar 

  6. Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844–2850.

    Google Scholar 

  7. Saino A, Pomidossi G, Perondi R, et al. Intracoronary angiotensin II potentiates coronary sympathetic vasoconstriction in humans. Circulation 1997;96:148–153.

    Google Scholar 

  8. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 1990;265:22348–22357.

    Google Scholar 

  9. Rajagopalan S, Brook R, Mehta RH, Supiano M, Pitt B. Effect of losartan in aging-related endothelial impairment. Am J Cardiol 2002;89:562–566.

    Google Scholar 

  10. Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation 1989;79:93–100.

    Google Scholar 

  11. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–1115.

    Google Scholar 

  12. Campisi R, Czernin J, Schoder H, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation 1998;98:119–125.

    Google Scholar 

  13. Preumont N, Lenaers A, Goldman S, et al. Coronary vasomotility and myocardial blood flow early after heart transplantation. Am J Cardiol 1996;78:550–554.

    Google Scholar 

  14. Grandin C, Wijns W, Melin JA, et al. Delineation of myocardial viability with PET. J Nucl Med 1995;36:1543–1552.

    Google Scholar 

  15. Vanoverschelde JL, Melin JA, Bol A, et al. Regional oxidative metabolism in patients after recovery from reperfused anterior myocardial infarction. Relation to regional blood flow and glucose uptake. Circulation 1992;85:9–21.

    Google Scholar 

  16. Bol A, Melin JA, Vanoverschelde JL, et al. Direct comparison of [13N]ammonia and [150]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres. Circulation 1993;87:512–525.

    Google Scholar 

  17. Di Carli M, Czernin J, Hoh CK, et al. Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. Circulation 1995;91:1944–1951.

    Google Scholar 

  18. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 1986;8:37–44.

    Google Scholar 

  19. Joannides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995;91:1314–1319.

    Google Scholar 

  20. Hornig B, Landmesser U, Kohler C, et al. Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: Role of superoxide dismutase. Circulation 2001;103:799–805.

    Google Scholar 

  21. Zeiher AM, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991;83:391–401.

    Google Scholar 

  22. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Jr., Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948–954.

    Google Scholar 

  23. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899–1906.

    Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium

    Nicolas Preumont, Philippe Unger & Guy Berkenboom

  2. PET/Biomedical Cyclotron Unit, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, B-1070, Brussels, Belgium

    Serge Goldman

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  1. Nicolas Preumont
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  2. Philippe Unger
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  3. Serge Goldman
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  4. Guy Berkenboom
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Preumont, N., Unger, P., Goldman, S. et al. Effect of Long-Term Angiotensin II Type I Receptor Antagonism on Peripheral and Coronary Vasomotion. Cardiovasc Drugs Ther 18, 197–202 (2004). https://doi.org/10.1023/B:CARD.0000033640.17844.4b

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  • DOI: https://doi.org/10.1023/B:CARD.0000033640.17844.4b

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