ROLE OF ANGIOTENSIN-II IN BLOOD-PRESSURE REGULATION AND IN THE PATHOPHYSIOLOGY OF CARDIOVASCULAR DISORDERS

Angiotensin II (Ang II) raises blood pressure (BP) by a number of actions, the most important ones being vasoconstriction, sympathetic nervous stimulation, increased aldosterone biosynthesis and renal actions. Other Ang II actions include induction of growth, cell migration, and mitosis of vascular smooth muscle cells, increased synthesis of collagen type I and III in fibroblasts, leading to thickening of the vascular wall and myocardium, and fibrosis. These actions are mediated by type 1 Ang II receptors (AT(1)), and may be blocked by losartan, a specific blocker of AT(1) receptors. In particular, studies employing losartan have shown that Ang II is an important contributor to BP regulation and plays a significant role in hypertension and in the pathophysiology of vascular damage during the course of hypertension. Ang II is also involved in the process of atherosclerosis and in remodelling and repair processes of the myocardium following myocardial infarction. Finally, increased Ang II is an important part of neurohumoral activation in heart failure. Exciting new discoveries concerned with polymorphisms of genes coding for angiotensin converting enzyme (ACE) and angiotensinogen suggest that Ang II may be genetically associated with increased risk for myocardial infarction, hypertension and left ventricular hypertrophy.