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[ACE inhibition: mechanisms of cardioprotection in heart hypertrophy]
1Medizinische Klinik und Poliklinik B - Kardiologie, Pneumologie und Angiologie, Heinrich-Heine-Universität Düsseldorf.
Insights
Left ventricular hypertrophy in arterial hypertension is a risk factor for cardiac failure. Sympatholytic therapy, unlike other antihypertensives, effectively reverses this hypertrophy, suggesting catecholamines play a key role.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Context:
- Arterial hypertension is linked to left ventricular hypertrophy (LVH), a significant risk factor for cardiac failure.
- Antihypertensive strategies should focus on preventing or regressing LVH.
- Blood pressure reduction alone does not guarantee LVH reversal.
Purpose:
- To investigate the role of catecholamines and the renin-angiotensin system in myocardial hypertrophy.
- To evaluate the efficacy of different antihypertensive therapies in reversing LVH.
- To test the hypothesis that catecholamines influence myocardial hypertrophy independently of blood pressure.
Summary:
- Vasodilators (hydralazine, minoxidil) did not reduce LVH, despite increasing norepinephrine.
- Sympatholytic therapy with methyldopa reversed LVH in spontaneously hypertensive rats.
- Norepinephrine at subhypertensive doses induced LVH, supporting a catecholamine-driven hypertrophy hypothesis.
- The renin-angiotensin system also exhibits trophic effects on the myocardium.
- Clinical studies show LVH regression with sympatholytics, ACE inhibitors, calcium channel blockers, and beta blockers.
- Diuretics did not decrease LVH even with normalized blood pressure.
Impact:
- Highlights the critical role of catecholamines in myocardial hypertrophy, independent of blood pressure.
- Identifies specific antihypertensive drug classes (sympatholytics, ACE inhibitors, etc.) effective for LVH regression.
- Suggests targeted therapies are crucial for managing hypertensive heart disease and preventing cardiac failure.
Abstract:
Epidemiologic studies have revealed that in arterial hypertension left ventricular hypertrophy is an important risk factor for cardiac failure. Accordingly antihypertensive therapy should aim at preventing or regressing left ventricular hypertrophy. Reduction of blood pressure does not necessarily induce reversal of left ventricular hypertrophy. Vasodilators like hydralazine and minoxidil, which lead to augmented plasma levels of norepinephrine, were not able to diminish left ventricular hypertrophy. In contrast, a sympatholytic therapy with methyldopa caused a reversal of left ventricular muscle mass. These experimental findings in spontaneously hypertensive rats led to the hypothesis that catecholamines control the onset and progression of myocardial hypertrophy mostly independent of blood pressure. This hypothesis was supported by the experimental findings, that subhypertensive dosages of norepinephrine induce left ventricular hypertrophy and that this hormone promotes alpha-receptor mediated growth of isolated myocytes. Recent studies have revealed that also the renin-angiotension-system has trophic effect on the myocardium. Clinical investigations have documented regression of cardiac hypertrophy due to antihypertensive therapy with sympatholytic drugs, ACE-inhibitors, calcium-channel blockers and beta-receptor blockers. Diuretics failed to decrease left ventricular muscle mass along with blood pressure normalization.