Skip to main content
NCBI home page
British Heart Journal logoLink to British Heart Journal
. 1989 Jan;61(1):23–28. doi: 10.1136/hrt.61.1.23

Effects of enalapril on myocardial noradrenaline overflow during exercise in patients with chronic heart failure.

I P Mulligan 1, A G Fraser 1, M J Lewis 1, A H Henderson 1
PMCID: PMC1216616  PMID: 2537095

Abstract

The effects of the angiotensin converting enzyme inhibitor enalapril on myocardial sympathetic tone, as represented by noradrenaline overflow, were studied in 14 men with congestive heart failure (mean ejection fraction 20%) in a double blind crossover comparison with placebo. Arterial and coronary sinus catecholamine concentrations and oxygen content, and coronary sinus blood flow, were measured at rest and during peak symptom limited upright exercise on a bicycle ergometer. There were no significant changes four hours after the first dose of enalapril, but after six weeks of treatment (10-20 mg/day) enalapril reduced myocardial overflow of noradrenaline at peak exercise. The external workload (exercise duration) increased from baseline values after both placebo and enalapril, and there was no difference between placebo and enalapril at six weeks. Heart work, however, was lower after enalapril: stroke work index was reduced at rest and the double product was lower at peak exercise. The reduction in maximal myocardial oxygen consumption after enalapril did not reach statistical significance. Coronary sinus adrenaline concentrations after enalapril and after placebo were not significantly different. The long term reduction of myocardial sympathetic activity on exercise may represent a significant benefit from angiotensin converting enzyme inhibition in heart failure and may reflect a reduced cardiac workload.

Full text

PDF
23

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baim D. S., Rothman M. T., Harrison D. C. Improved catheter for regional coronary sinus flow and metabolic studies. Am J Cardiol. 1980 Dec 1;46(6):997–1000. doi: 10.1016/0002-9149(80)90357-4. [DOI] [PubMed] [Google Scholar]
  2. Bristow M. R., Ginsburg R., Minobe W., Cubicciotti R. S., Sageman W. S., Lurie K., Billingham M. E., Harrison D. C., Stinson E. B. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982 Jul 22;307(4):205–211. doi: 10.1056/NEJM198207223070401. [DOI] [PubMed] [Google Scholar]
  3. Bristow M. R. The adrenergic nervous system in heart failure. N Engl J Med. 1984 Sep 27;311(13):850–851. doi: 10.1056/NEJM198409273111310. [DOI] [PubMed] [Google Scholar]
  4. Cleland J. G., Dargie H. J., Ball S. G., Gillen G., Hodsman G. P., Morton J. J., East B. W., Robertson I., Ford I., Robertson J. I. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state. Br Heart J. 1985 Sep;54(3):305–312. doi: 10.1136/hrt.54.3.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cleland J. G., Dargie H. J., Robertson J. I., Ball S. G., Hodsman G. P. The use of captopril in the management of cardiac failure. Scott Med J. 1984 Apr;29(2):129–130. [PubMed] [Google Scholar]
  6. Clough D. P., Collis M. G., Conway J., Hatton R., Keddie J. R. Interaction of angiotensin-converting enzyme inhibitors with the function of the sympathetic nervous system. Am J Cardiol. 1982 Apr 21;49(6):1410–1414. doi: 10.1016/0002-9149(82)90352-6. [DOI] [PubMed] [Google Scholar]
  7. Cody R. J., Franklin K. W., Kluger J., Laragh J. H. Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute and long-term converting-enzyme inhibition. Circulation. 1982 Jul;66(1):135–142. doi: 10.1161/01.cir.66.1.135. [DOI] [PubMed] [Google Scholar]
  8. Cohn J. N., Levine T. B., Olivari M. T., Garberg V., Lura D., Francis G. S., Simon A. B., Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984 Sep 27;311(13):819–823. doi: 10.1056/NEJM198409273111303. [DOI] [PubMed] [Google Scholar]
  9. Convertino V. A., Keil L. C., Bernauer E. M., Greenleaf J. E. Plasma volume, osmolality, vasopressin, and renin activity during graded exercise in man. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jan;50(1):123–128. doi: 10.1152/jappl.1981.50.1.123. [DOI] [PubMed] [Google Scholar]
  10. Creager M. A., Halperin J. L., Bernard D. B., Faxon D. P., Melidossian C. D., Gavras H., Ryan T. J. Acute regional circulatory and renal hemodynamic effects of converting-enzyme inhibition in patients with congestive heart failure. Circulation. 1981 Sep;64(3):483–489. doi: 10.1161/01.cir.64.3.483. [DOI] [PubMed] [Google Scholar]
  11. Daly P., Rouleau J. L., Cousineau D., Burgess J. H., Chatterjee K. Effects of captopril and a combination of hydralazine and isosorbide dinitrate on myocardial sympathetic tone in patients with severe congestive heart failure. Br Heart J. 1986 Aug;56(2):152–157. doi: 10.1136/hrt.56.2.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Edwards C. R., Padfield P. L. Angiotensin-converting enzyme inhibitors: past, present, and bright future. Lancet. 1985 Jan 5;1(8419):30–34. doi: 10.1016/s0140-6736(85)90975-4. [DOI] [PubMed] [Google Scholar]
  13. Ekelund L. G. Circulatory and respiratory adaptation during prolonged exercise of moderate intensity in the sitting position. Acta Physiol Scand. 1967 Apr;69(4):327–340. doi: 10.1111/j.1748-1716.1967.tb03529.x. [DOI] [PubMed] [Google Scholar]
  14. Eriksson B. M., Persson B. A. Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography with electrochemical detection. J Chromatogr. 1982 Mar 12;228:143–154. doi: 10.1016/s0378-4347(00)80427-2. [DOI] [PubMed] [Google Scholar]
  15. Francis G. S., Goldsmith S. R., Cohn J. N. Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. Am Heart J. 1982 Oct;104(4 Pt 1):725–731. doi: 10.1016/0002-8703(82)90003-5. [DOI] [PubMed] [Google Scholar]
  16. Francis G. S., Goldsmith S. R., Ziesche S., Nakajima H., Cohn J. N. Relative attenuation of sympathetic drive during exercise in patients with congestive heart failure. J Am Coll Cardiol. 1985 Apr;5(4):832–839. doi: 10.1016/s0735-1097(85)80420-4. [DOI] [PubMed] [Google Scholar]
  17. Goldsmith S. R., Francis G. S., Levine T. B., Cohn J. N. Regional blood flow response to orthostasis in patients with congestive heart failure. J Am Coll Cardiol. 1983 Jun;1(6):1391–1395. doi: 10.1016/s0735-1097(83)80041-2. [DOI] [PubMed] [Google Scholar]
  18. Halter J. B., Kelley K. O., Gould K. L. Cardiac uptake and secretion of catecholamines during adrenergic stimulation in vivo. Am J Physiol. 1982 Jul;243(1):E52–E58. doi: 10.1152/ajpendo.1982.243.1.E52. [DOI] [PubMed] [Google Scholar]
  19. Hasking G. J., Esler M. D., Jennings G. L., Burton D., Johns J. A., Korner P. I. Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation. 1986 Apr;73(4):615–621. doi: 10.1161/01.cir.73.4.615. [DOI] [PubMed] [Google Scholar]
  20. Hills M., Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol. 1979 Jul;8(1):7–20. doi: 10.1111/j.1365-2125.1979.tb05903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kramer B. L., Massie B. M., Topic N. Controlled trial of captopril in chronic heart failure: a rest and exercise hemodynamic study. Circulation. 1983 Apr;67(4):807–816. doi: 10.1161/01.cir.67.4.807. [DOI] [PubMed] [Google Scholar]
  22. Magorien R. D., Leier C. V., Kolibash A. J., Barbush T. J., Unverferth D. V. Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure. Circulation. 1984 Nov;70(5):884–890. doi: 10.1161/01.cir.70.5.884. [DOI] [PubMed] [Google Scholar]
  23. Manhem P., Lecerof H., Hökfelt B. Plasma catecholamine levels in the coronary sinus, the left renal vein and peripheral vessels in healthy males at rest and during exercise. Acta Physiol Scand. 1978 Nov;104(3):364–369. doi: 10.1111/j.1748-1716.1978.tb06288.x. [DOI] [PubMed] [Google Scholar]
  24. Mathey D. G., Chatterjee K., Tyberg J. V., Lekven J., Brundage B., Parmley W. W. Coronary sinus reflux. A source of error in the measurement of thermodilution coronary sinus flow. Circulation. 1978 Apr;57(4):778–786. doi: 10.1161/01.cir.57.4.778. [DOI] [PubMed] [Google Scholar]
  25. Mulligan I. P., Fraser A. G., Tirlapur V., Lewis M. J., Newcombe R. G., Henderson A. H. A randomized cross-over study of enalapril in congestive heart failure: haemodynamic and hormonal effects during rest and exercise. Eur J Clin Pharmacol. 1988;34(4):323–331. doi: 10.1007/BF00542431. [DOI] [PubMed] [Google Scholar]
  26. Packer M. Vasodilator and inotropic therapy for severe chronic heart failure: passion and skepticism. J Am Coll Cardiol. 1983 Nov;2(5):841–852. doi: 10.1016/s0735-1097(83)80230-7. [DOI] [PubMed] [Google Scholar]
  27. Rubin S. A., Siemienczuk D., Nathan M. D., Prause J., Swan H. J. Accuracy of cardiac output, oxygen uptake, and arteriovenous oxygen difference at rest, during exercise, and after vasodilator therapy in patients with severe, chronic heart failure. Am J Cardiol. 1982 Nov;50(5):973–978. doi: 10.1016/0002-9149(82)90404-0. [DOI] [PubMed] [Google Scholar]
  28. Swedberg K., Hjalmarson A., Holmberg S. Effects of work and acute beta-receptor blockade on myocardial noradrenaline release in congestive cardiomyopathy. Clin Cardiol. 1979 Dec;2(6):424–430. doi: 10.1002/clc.4960020607. [DOI] [PubMed] [Google Scholar]
  29. Swedberg K., Viquerat C., Rouleau J. L., Roizen M., Atherton B., Parmley W. W., Chatterjee K. Comparison of myocardial catecholamine balance in chronic congestive heart failure and in angina pectoris without failure. Am J Cardiol. 1984 Oct 1;54(7):783–786. doi: 10.1016/s0002-9149(84)80208-8. [DOI] [PubMed] [Google Scholar]
  30. Thomas J. A., Marks B. H. Plasma norepinephrine in congestive heart failure. Am J Cardiol. 1978 Feb;41(2):233–243. doi: 10.1016/0002-9149(78)90162-5. [DOI] [PubMed] [Google Scholar]
  31. Viquerat C. E., Kereiakes D., Morris D. L., Daly P. A., Wexman M., Frank P., Parmley W. W., Chatterjee K. Alterations in left ventricular function, coronary hemodynamics and myocardial catecholamine balance with MDL 17043, a new inotropic vasodilator agent, in patients with severe heart failure. J Am Coll Cardiol. 1985 Feb;5(2 Pt 1):326–332. doi: 10.1016/s0735-1097(85)80054-1. [DOI] [PubMed] [Google Scholar]
  32. Yamaguchi N., de Champlain J., Nadeau R. Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog. Circ Res. 1975 May;36(5):662–668. doi: 10.1161/01.res.36.5.662. [DOI] [PubMed] [Google Scholar]
  33. Zimmerman B. G. Adrenergic facilitation by angiotensin: does it serve a physiological function? Clin Sci (Lond) 1981 Apr;60(4):343–348. doi: 10.1042/cs0600343. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES