Angiotensin II Receptor Subtypes in the Kidney1

The kidney is an important target organ for angiotensin II. The diverse biologic effects of angiotensin II in the kidney and periphery suggest that angiotensin II may be interacting with more than one receptor. Recently, the synthesis of highly selective nonpeptide angiotensin II receptor antagonists and the expression cloning of the angiotensin receptor have unequivocally demonstrated the existence of at least two angiotensin Ii receptor subtypes, designated AT1 and AT2. Autoradiography and ligand binding studies have shown that most tissues, including the kidney, have a mixture of both receptor subtypes. The AT1 receptor is coupled via G proteins to traditional signal transduction mechanisms such as stimulation of phospholipase C, Ca2 mobilization, and inhibition of adenylate cyclase. The AT2 receptor does not appear to be coupled to G proteins, and the signal transduction pathway(s) associated with this receptor is not known but may involve cGMP. In the kidney, as in the periphery, all of the major physiologic actions of angiotensin II appear to be mediated by activation of the AT1 receptor. In this review, the general characteristics of the AT1 and AT2 receptors and their distribution and function in the kidney will be discussed.