The role of the AT1 receptor in the cardiovascular continuum

Abstract

The renin-angiotensin system plays a pivotal role in many cardiovascular diseases. Angiotensin II mediates most of its relevant biological effects via angiotensin II type-1 (AT 1 ) receptor activation. AT 1 -receptor activation not only elevates blood pressure but also leads to initiation of early vascular dysfunction and cardiac hypertrophy. Long-lasting hypertension, together with additional risk factors, frequently results in coronary artery disease and myocardial infarction associated with high morbidity and mortality. Stimulation of AT 1 receptors not only propagates underlying atherosclerosis, but is also important in cardiac remodeling after myocardial infarction. Finally, patients with hypertension and/or myocardial infarction are at risk of developing heart failure, the ultimate endpoint of the cardiovascular continuum. AT 1 -receptor activation increases loss of intact myocardium, enhances cardiac afterload and water/salt retention, and has a detrimental influence on renal and metabolic function. Inhibition of the renin-angiotensin system by ACE inhibitors or AT 1 -receptor blockers lowers blood pressure and has a significant beneficial impact on atherosclerotic lesions and hypertensive cardiac damage. In addition, it diminishes cardiac remodeling after myocardial infarction and ameliorates clinical symptoms and reduces mortality in heart failure. These findings underline the potential importance of AT 1 -receptor antagonists as protective drugs in virtually all stages of the cardiovascular continuum.