Angiotensin II receptor pharmacology and AT₁-receptor blockers

Abstract

Angiotensin II (Ang II) has diverse physiological actions leading, for example, to increases in extracellular volume, peripheral vascular resistance and blood pressure, and has also been implicated in the regulation of cell growth and differentiation. Molecular cloning and pharmacological studies have defined two major classes of Ang II receptors, designated as AT₁ and AT₂. Most effects of Ang II are mediated by AT₁ receptors. Much less is known about the physiological role of AT₂ receptors. Recent evidence suggests involvement of AT₂ receptors in development, cell differentiation, apoptosis and regeneration in various tissues. AT₁ and AT₂ receptors have been shown to exert counteracting effects on cellular growth and differentiation, vascular tone and the release of arginine vasopressin (AVP). In each condition the AT₂ receptor appears to down-modulate actions mediated by the AT₁ receptor, resulting in decreased cellular proliferation, decreased levels of serum AVP levels or decreased vasoconstrictor responses. In addition, in neuronal cell lines, the AT₂ receptor reportedly exerts antiproliferative effects and promotes neurite outgrowth, an effect accompanied by significant changes in the gene expression pattern of growth- and differentiation-related genes.