Review Article Korean Circulation J 2000;308:1045-1054 심부전증의최신개념과치료 김재중 New Concepts and Treatment of Heart Failure Modulation of Neurohormonal System Jae-Joong Kim, MD, PhD Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea Activation of Neurohormnal Systems in Heart Failure 1045
Fig. 1. Activation of neurohormonal system in heart failure. Renin-Angiotensin-Aldosterone System (RAAS) Table 1. Adverse effects of angiotensin in congestive heart failure Left ventricular structural and functional effects Increased transmural wall stress Dilation caused by increase of end-diastolic and endsystolic volumes Decreased coronary flow in epicardial and transmural vessels Hemodynamic effects Increased vascular resistance Positive Inotropic stimulation Neurohormonal and paracrine effects Increased tissue effects of angiotensin Stimulation of aldosterone production, with sodium and volume retention Increase of circulatory catecholamines, impaired baroreceptor function, and abnormal Sympathetic-parasympathetic balance Increased bradykinin degradation Stimulate the secretion of arginine vasopressin Mitogenic and growth effects Myocardial hypertrophy Vascular smooth muscle hypertrophy Cell protein enhancement Angiotensin con-verting enzyme (ACE) inhibitor 1046 Korean Circulation J 2000;308:1045-1054
Table 2. Effects of Ace inhibitors in patients with congestive heart failure Study No. Age CAD EF Class Drugs F/U Mortality reduction CONSENSUS 253 70 74% N/A Enalapril 1 88 days 27%p0.003 V-HeFT 804 61 53% 29%, Enalapril 2.5 years 28%p0.002 SOLVD treat. 2569 61 70% 25%, Enalapril 41.1 mos. 16%p0.004 SOLVD prev. 4228 59 83% 28%, Enalapril 37.4 mos. 8%p0.30 Evaluation of ACE inhibitor dose in CHF Angiotensin Ⅱ receptor blocker 1047
Fig. 2. Cascades of RAS and mechanism of action of ACE inhibitors and AT1 receptor antagonists. ATAngiotensin receptorst-patissue plasminogen activatorsnssympathetic nervous systemgrowth Fgrowth factorspaiplasminogen activator inhibitor. Table 3. Angiotensin receptor subtypeeffect Angiotesin R subtype Angiotensin R subtype Fibrosis Vasoconstriction Matrix growth PA-I synthesis Endothelial dysfunction 1048 Nitric oxide release Antiproliferative effect Apoptosis Korean Circulation J 2000;308:1045-1054
Fig. 3. Stimuli generating aldosterone. Aldosterone antagonist Fig. 4. The results of RALES. 1049
Fig. 5. Harmful effect of prolonged sympathetic stimulation on cardiac myocytes. 1050 Sympathetic System Harmful effect of prolonged sympathetic stimulation in heart failure Effects of β-blockers in heart failure Korean Circulation J 2000;308:1045-1054
Clinical use of β-blocker in heart failure 1051
Endothelin System Fig. 6. -Blocker Effects on Mortality in CHF. Fig. 8. -blocker Effects on Combination in CHF. Fig. 7. -blocker Effects on Hospitalization in CHF. Fig. 9. Generation of endothelin-1. 1052 Korean Circulation J 2000;308:1045-1054
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