Benefits of the RAS blockade: clinical evidence before the ONTARGET study.

Activation of the AT1 angiotensin II (Ang II) receptors has various effects including vasoconstriction, hypertrophy, and possibly hyperplasia of vascular smooth muscle cells and cardiomyocytes and increase in extracellular collagen matrix synthesis. These actions lead to the development of cardiovascular hypertrophy and fibrosis, as well as arterial stiffness, which are some key factors in the development of the cardiovascular and renal complications. In clinical studies, it has been shown that renin-angiotensin blockade has direct and specific implications in the evolution of heart failure, coronary disease, stroke, and hypertensive and diabetic renal disease. The beneficial cardiovascular and renal effects of blocking the renin-angiotensin-aldosterone system reported in numerous clinical trials may be at least partially related to the actions of these drugs on cardiovascular and renal fibrosis, and arterial stiffness. These effects are now well-established and lead the international medical societies to propose the use of the renin-angiotensin system (RAS) blockers as initial treatment (both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers) in several cardiovascular, metabolic, and renal disorders such as hypertension, heart failure, and proteinuria.