Angiotensin-converting enzyme inhibition and endothelial dysfunction: Focus on ramipril

European Heart Journal, Supplement 01/2003; 5. DOI: 10.1016/S1520-765X(03)90061-7
Source: OAI


Endothelial cells are strategically located between the circulating blood and the vascular smooth muscle. Through release of numerous vasoactive substances, they are crucially involved in regulating the functions of vascular smooth muscle and circulating blood cells. Important endothelium-delivered vasodilators include prostacyclin, bradykinin, endothelium-derived hyperpolarising factor, and nitric oxide. Nitric oxide inhibits cellular growth and migration, and acts in concert with prostacyclin to exert potent antiatherogenic and antithrombotic effects. These effects are counterbalanced by endothelial vasoconstrictors, such as reactive oxygen species, endothelin-1, and angiotensin II, which exert pro-thrombotic, inflammatory, and growth-promoting properties. Cardiovascular risk factors cause cardiovascular disease by causing endothelial dysfunction; thus, modern therapeutic strategies focus on preserving or restoring endothelial integrity. In addition to their role in inhibiting the renin-angiotensin system, angiotensin-converting enzyme (ACE) inhibitors prolong the half-life of bradykinin and stabilize the bradykinin receptor linked to formation of nitric oxide. Chronic ACE inhibition improves endothelial function in patients with cardiovascular risk. This may explain why patients treated with ACE inhibitors experience a greater cardiovascular benefit than is attributable to the decrease in blood pressure. Whether and to what degree improvement of endothelial dysfunction translates into clinical benefits for patients with cardiovascular disease remains to be determined.

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    ABSTRACT: Endothelial dysfunction is caused by risk factors, which have basic, and initial role in atherogenesis. During further progression it is still not known, whether is and how is endothelial dysfunction influenced by risk factors in the late phase of atherosclerosis and/or what kind of other factors play role in endothelial dysfunction. Brachial artery flow mediated vasodilation was examined in 293 high risk patients (vascular 2. type diabetes patients/persons with + 2 risk factors). Relationship between endothelial function and risk factors, and risk stratifications were statistically examined to define the principal predictors of endothelial dysfunction. 1. Examination of flow mediated vasodilation of brachial artery with ultrasound machine, 2. Risk factors evaluating, 3. Vascular examinations: physical, exercise test, Holter monitoring, CW Doppler, duplex scan 4. Risk stratification (10 year risk of fatal vascular events), 5. Statistical analysis (comparative and cohort). 1. Mean endothelial function of 293 high risk patients was reduced (105.1%). 2. Vascular disease plays principal role of the endothelial function in late phase atherosclerosis, because significantly decreases the brachial artery vasodilation (104.3% v. 108.3% p < 0.01) and significantly more (p < 0.0009) endothelial dysfunction can be found in patients with vascular disease than without. 3. Bad risk stratification plays principal role too, because there are significantly (p = 0.012) more endothelial dysfunction in high risk patients, than with better risk stratification. 4. Lipid-, glucose-metabolic alterations, hypertension, age and smoking (all: p = NS) have not already any role in endothelial dysfunction in late phase atherosclerosis. Role of risk factors in initial atherogenesis is scientific evidence, but the role of these factors can not be proved later, when endothelial dysfunction already evolved. In this phase of atherosclerosis the vascular disease and the bed risk stratification have principal role, because they can cause significant more reduction of already reduced endothelial function. Further studies necessary to determine, whether this statistically proved relationship have, or have not any clinical relevance.
    Orvosi Hetilap 01/2006; 147(3):99-106.
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    ABSTRACT: Subjects with peripheral arterial disease (PAD) of the lower limbs are at high risk for cardiovascular and cerebrovascular events and the prevalence of coronary artery disease in such patients is elevated. Recent studies have shown that regular use of cardiovascular medications, such as therapeutic and preventive agents for PAD patients, seems to be promising in reducing long-term mortality and morbidity. The angiotensin-converting-enzyme (ACE) system plays an important role in the pathogenesis and progression of atherosclerosis, and ACE-inhibitors (ACE-I) seem to have vasculoprotective and antiproliferative effects as well as a direct anti-atherogenic effect. ACE-I also promote the degradation of bradykinin and the release of nitric oxide, a potent vasodilator; further, they have shown important implications for vascular oxidative stress. Other studies have suggested that ACE-I may also improve endothelial dysfunction. ACE-I are useful for reducing the risk of cardiovascular events in clinical and subclinical PAD. Particularly, one agent of the class (ie, ramipril) has shown in many studies to able to significantly reduce cardiovascular morbidity and mortality in patients with PAD.
    Vascular Health and Risk Management 02/2008; 4(6):1179-87.
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    ABSTRACT: There is mounting evidence that dysfunction of the renin angiotensin system is a vital contributor to the development of atherosclerosis. Nonetheless, the efficacy of angiotensin receptor blockers on clinical outcomes in patients with coronary atherosclerosis has been limited. This review will examine the potential mechanisms by which angiotensin receptor blockers potentially affect several key steps in the atherosclerotic process: endothelial function, inflammation, and thrombosis. Despite the mounting evidence for these agents on multiple processes in the development of atherosclerosis, their clinical utility in patients with coronary artery disease remains unclear.
    The American Journal of the Medical Sciences 10/2008; 336(3):270-7. DOI:10.1097/MAJ.0b013e31816d1dc5 · 1.39 Impact Factor

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