PHYSIOLOGICAL AND PHARMACOLOGICAL IMPLICATIONS OF AT(1) VERSUS AT(2) RECEPTORS

Angiotensin II (Ang II) has diverse physiological actions that lead, f or instance, to increases in extracellular volume and peripheral vascu lar resistance and blood pressure, and it has also been implicated in the regulation of cell growth and differentiation. Molecular cloning a nd pharmacological studies have defined two major classes of Ang II re ceptors, designated AT, and AT(2). Most effects of Ang II are mediated by AT(1) receptors. Much less is known about the physiological role o f AT(1) receptors. Recent evidence suggests involvement of AT(2) recep tors in development, cell differentiation, apoptosis, and regeneration in various tissues. AT(1) and AT(2) receptors have been shown to exer t counteracting effects on cellular growth and differentiation, vascul ar tone, and the release of arginine vasopressin. In each condition, t he AT(2) receptor appears to down-modulate actions mediated by the AT( 1) receptor, resulting in decreased cellular proliferation, decreased levels of serum arginine vasopressin levels, or decreased vasoconstric tor responses. In addition, in neuronal cell lines, the AT(2) receptor exerts antiproliferative actions and promotes neurite outgrowth, an e ffect accompanied by significant changes in the expression pattern of growth/differentiation-related genes.