Institute of Pharmacology, University of Kiel, Kiel, Germany, and Medical College of Wisconsin, Madison, Wisconsin, USA

Correspondence: Thomas Unger, M.D., Institute of Pharmacology, University of Kiel, Hospitalstr. 4, D-24105 Kiel, Germany. E-mail: th.unger@pharmakologie.uni-kiel.de

Abstract

Physiological and pharmacological implications of AT₁ versus AT₂receptors. Angiotensin II (Ang II) has diverse physiological actions that lead, for instance, to increases in extracellular volume and peripheral vascular resistance and blood pressure, and it 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 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. 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 arginine vasopressin levels, or decreased vasoconstrictor responses. In addition, in neuronal cell lines, the AT₂ receptor exerts antiproliferative actions and promotes neurite outgrowth, an effect accompanied by significant changes in the expression pattern of growth/differentiation-related genes.