Blood pressure lowering and renin-angiotensin system blockade.

Abstract

Angiotensin II (ANG II), the main effector peptide of the renin-angiotensin system (RAS), is implicated in the development of vascular, cardiac and renal pathologies. Considered to be central to the whole cardiovascular continuum, recent investigations have also established a role for ANG II in the recovery of the brain after cerebral insult. ANG II exerts its actions through two receptors: ANG II type 1 (AT1) and type 2 (AT2). Characterization of these receptors and their functions has led to an understanding of the role that ANG II plays in the body and has opened new avenues for therapeutic research. Investigations in animal models of hypertension, endothelial dysfunction, myocardial infarction, left ventricular hypertrophy and stroke have established the part that the ANG II receptors play in vascular, cardiac and cerebral pathologies using selective inhibitors of AT1 and AT2 receptors. The AT1 receptor mediates most of the deleterious effects of ANG II, such as vasoconstriction, endothelial damage and cell growth. Selective inhibition of the AT1 receptor not only inhibits these effects, but also leaves the AT2 receptor open to stimulation by ANG II. Among the many potential effects mediated by stimulation of the AT2 is the neuronal regeneration after injury and inhibition of pathological growth. Thus, AT1 receptor blockade appears to offer both active and passive therapeutic benefits. With high penetration through the blood-brain barrier, effective and selective inhibition of the AT1 receptor and prolonged duration of the receptor blockade for more than 24 h, telmisartan is strongly placed for the emerging therapeutic opportunities.