EXP3174, the AII antagonist human metabolite of losartan, but not losartan nor the angiotensin-converting enzyme inhibitor captopril, prevents the development of lethal ischemic ventricular arrhythmias in a canine model of recent myocardial infarction

Journal of the American College of Cardiology

Volumn 34, Issue 3, 1999, Pages 876-884

  Lynch Jr , Joseph J ^a   Stump, Gary L ^a   Wallace, Audrey A ^a   Painter, Carla A ^a   Thomas, Justina M ^a   Kusma, Sandra E ^a   Gould, Robert J ^a   Grossman, William ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 BUTYL 4 CHLORO 1 [[2' (1H TETRAZOL 5 YL) 4 BIPHENYLYL]METHYL] 5 IMIDAZOLECARBOXYLIC ACID; ANGIOTENSIN ANTAGONIST; CAPTOPRIL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; LOSARTAN;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOG; DRUG MECHANISM; ELDERLY CARE; FEMALE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEART VENTRICLE ARRHYTHMIA; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRAVENOUS DRUG ADMINISTRATION; MALE; NONHUMAN; PLASMA RENIN ACTIVITY; PRIORITY JOURNAL;

ANALYSIS OF VARIANCE; ANGIOTENSIN II; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; ARRHYTHMIA; CAPTOPRIL; DISEASE MODELS, ANIMAL; DOGS; DRUG EVALUATION, PRECLINICAL; FEMALE; HEART VENTRICLES; HUMANS; IMIDAZOLES; LOSARTAN; MALE; MYOCARDIAL INFARCTION; MYOCARDIAL ISCHEMIA; TETRAZOLES; TIME FACTORS;

EID: 0032851022     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0735-1097(99)00253-3     Document Type: Article

References (48)

1. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian enalapril survival study (CONSENSUS). N Engl J Med. 316:1987;1429-1435.
2. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 325:1991;293-302.
3. Pfeffer M.A., Braunwald E., Moye L.A., 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. The SAVE Investigators. N Engl J Med. 327:1992;669-677.
4. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 342:1993;821-828.
5. Kober L., Torp-Pedersen C., Carlsen J.E., et al. A clinical trial of the angiotensin converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 333:1995;1670-1676.
6. Cleland J.G.F., Erhardt L., Murray G., Hall A.S., Ball S.G. Eur Heart J. 8:1997;41-51.
7. Waldo A.L., Camm A.J., deRuyter H. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet. 348:1996;7-12.
8. Packer M. Lack of correlation between ventricular arrhythmias and sudden death in patients with chronic heart failure. Circulation. 85:(Suppl I):1992;50-56.
9. Pahor M., Gambassi G., Carbonin P. Antiarrhythmic effects of ACE inhibitors a matter of faith or reality? Cardiovasc Res. 28:1994;173-182.
10. Visser F.C., Visser C.A. Current controversies with ACE inhibitor treatment in heart failure. Cardiology. 87:(Suppl 1):1996;23-28.
11. Goodfriend T.L., Elliott M.E., Catt K.J. Angiotensin receptors and their antagonists. N Engl J Med. 334:1996;1649-1654.
12. Pitt B., Segal R., Martinez F.A. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet. 349:1997;747-752.
13. Thomas G.P., Ferrier G.R., Howlett S.E. Losartan exerts antiarrhythmic activity independent of angiotensin II receptor blockade in simulated ventricular ischemia and reperfusion. J Pharmacol Exp Ther. 278:1996;1090-1097.
14. Lee Y.-M., Peng Y.-Y., Ding Y.-A., Yen M.-H. Losartan attenuates myocardial ischemia-induced ventricular arrhythmias and reperfusion injury in spontaneously hypertensive rats. Am J Hypertens. 10:1997;852-858.
15. Matsuo K., Kumagai K., Annoura M., et al. Effects of an angiotensin II antagonist on reperfusion arrhythmias in dogs. PACE. 20:1997;938-945.
16. Patterson E., Holland K., Eller B.T., Lucchesi B.R. Ventricular fibrillation resulting from ischemia at a site remote from previous myocardial infarction. A conscious canine model of sudden coronary death. Am J Cardiol. 50:1982;1414-1423.
17. Lynch J.J., Wallace A.A., Stump G.L., Stupienski R.F., Kothstein T., Gehret J.R. Differential efficacy of the Class III agent MK-499 against programmed stimulation-induced and ischemia-induced ventricular arrhythmias in a canine model of previous myocardial infarction. J Pharmacol Exp Ther. 277:1996;671-678.
18. Wong P.C., Hart S.D., Duncia J.V., Timmermans P.B. Nonpeptide angiotensin II antagonists. Studies with Dup753 and EXP3174 in dogs. Eur J Pharmacol. 202:1991;323-330.
19. MacFadyen R.J., Tree M., Lever A.F., Reid J.L. Effects of the angiotensin II receptor antagonist losartan (Dup753/MK954) on arterial blood pressure, heart rate, plasma concentrations of angiotensin II and renin and the pressor response to infused angiotensin II in the salt-deplete dog. Clin Sci. 83:1992;549-556.
20. Brooks D.P., DePalma D., Ruffolo R.R. Effect of captopril and the nonpeptide angiotensin II antagonists SK&F108566 and EXP3174 on renal function in dogs with a renal artery stenosis. J Pharmacol Exp Ther. 263:1992;422-427.
21. Noda K., Sasaguri M., Ideishi M., Ikeda M., Arakawa K. Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs. Cardiovasc Res. 27:1993;334-340.
22. Dell'Italia L.J., Meng Q.C., Balcells E., Wei C.-C., Palmer R., Hageman G.R. Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces. J Clin Invest. 100:1997;253-258.
23. Ritter M.A., Furtek C.I., Lo M.-W. An improved method for the simultaneous determination of losartan and its major metabolite, EXP3174, in human plasma and urine by high performance liquid chromatography with fluorescence detection. J Pharmaceut Biomed Anal. 15:1997;1021-1029.
24. Ks in canine models of malignant ischemic ventricular arrhythmia. 1999, In Press.
25. Liang C., Gavras H., Black J., Sherman L.G., Hood W.B. Renin-angiotensin system inhibition in acute myocardial infarction in dogs. Effects on systemic hemodynamics, myocardial blood flow, segmental myocardial function and infarct size. Circulation. 66:1982;1249-1255.
26. McAlpine H.M., Cobbe S.M. Neuroendocrine change in acute myocardial infarction. Am J Med. 84:1988;61-66.
27. Packer M., Lee W.H., Kessler P.D., Gottlieb S.S., Bernstein J.L., Kukin M.L. Role of neurohumoral mechanisms in determining survival in patients with severe chronic heart failure. Circulation. 75:(Suppl IV):1987;80-92.
28. Dzau V, Pratt R. Cardiac, vascular and intrarenal renin-angiotensin systems in normal physiology and disease. In: Robertson JIS, Nicholls MG, eds. The Renin Angiotensin System. London, UK: Gower Medical Publishing; 1993:42.1-11.
29. Ikram H. The renin-angiotensin-aldosterone system and cardiac ischemia. Heart. 76:1996;60-67.
30. Squire IB, Reid JL. Interactions between the renin-angiotensin system and the autonomic nervous system. In: Robertson JIS, Nicholls MG, eds. The Renin Angiotensin System. London, UK: Gower Medical Publishing; 1993:37.1-16.
31. Emori T., Hirata Y., Schichiri M., Marumo F. Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun. 160:1989;93-100.
32. Chua B.H.L., Chua C.C., Diglio C.A., Siu B.B. Regulation of endothelin-1 messenger RNA by angiotensin II in rat heart endothelial cells. Biochim Biophys Acta. 1178:1993;201-206.
33. Allen I.S., Cohen N.M., Dhallan R.S., Gaa S.T., Lederer W.J., Rogers T.B. Angiotensin II increases spontaneous contractile frequency and simulates calcium current in cultured neonatal rat heart myocytes insights into the underlying biochemical mechanisms . Circ Res. 62:1988;524-534.
34. Nilius B., Tytgat J., Albitz R. Modulation of cardiac Na channels by angiotensin II. Biochim Biophys Acta. 1014:1989;259-262.
35. Morita H., Kimura J., Endoh M. Angiotensin II activation of a chloride current in rabbit cardiac myocytes. J Physiol. 483:1995;119-130.
36. Daleau P., Turgeon J. Angiotensin II modulates the delayed rectifier potassium current of guinea pig ventricular myocytes. Pflugers Arch. 427:1994;553-555.
37. to properties in cardiac ventricular myocytes. Circulation. 96:1997;I295.
38. De Mello WC, Crespo M.J. Cardiac refractoriness in rats is reduced by angiotensin II. J Cardiovasc Pharmacol. 25:1995;51-56.
39. de Langen C.D.J., de Graeff P.A., van Gilst W.H., Bel K.J., Kingma J.H., Wesseling H. Effects of angiotensin II and captopril on inducible sustained ventricular tachycardia two weeks after myocardial infarction in the pig. J Cardiovasc Pharmacol. 13:1989;186-191.
40. De Mello W., Altieri P. The role of the renin-angiotensin system in the control of cell communication in the heart effects of enalapril and angiotensin II . J Cardiovasc Pharmacol. 20:1992;643-651.
41. De Mello W.C. Renin-angiotensin system and cell communication in the failing heart. Hypertension. 27:1996;1267-1272.
42. Wong P., Price W.A., Chiu A.T., et al. Nonpeptide angiotensin II receptor antagonists. XI. Pharmacology of EXP3174 An active metabolite of DuP753, an orally active antihypertensive agent . J Pharmacol Exp Ther. 255:1990;211-217.
43. Lo M.-W., Goldberg M.R., McCrea J.B., Lu H., Furtek C.I., Bjornsson T.D. Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin Pharmacol Ther. 58:1995;641-649.
44. Christ DD, Kilkson T, Wong N, Lam G. Formation and disposition of EXP3174, a pharmacologically active metabolite of the novel angiotensin II receptor antagonist DuP753. Abstract of the 3rd North American Meeting of the International Society for the Study of Xenobiotics. 1990:464.
45. Christ D.D., Wong P.C., Wong Y.N., Hart S.D., Quon C.Y., Lam G.N. The pharmacokinetics and pharmacodynamics of the angiotensin II receptor antagonist losartan potassium (DuP753/MK954) in the dog. J Pharmacol Exp Ther. 268:1994;1199-1205.
46. Harada K., Komuro I., Hayashi D., Sugaya T., Murakami K., Yazaki Y. Angiotensin II type 1a receptor is involved in the occurrence of reperfusion arrhythmias. Circulation. 97:1998;315-317.
47. Wilber D.J., Lynch J.J., Montgomery D., Lucchesi B.R. Postinfarction sudden death. Significance of inducible ventricular tachycardia and infarct size in a conscious canine model. Am Heart J. 109:1985;8-18.
48. Rump L.C., Oberhauser V., Schwertfeger E., Schollmeyer P. Experimental evidence to support ELITE. Lancet. 351:1998;644-645.