Angiotensin II receptor subtypes in the kidney: Distribution and function

Summary: Angirotensin II (AII) is a powerful humoral regulator of body fluid and electrolyte balance and arterial blood pressure. In the kidney, All influences renal haemodynamics and proximal tubular reabsorption of sodium through activation of All that mediate complex signal transduction pathways. Angiotensin II is also implicated in the pathophysiological process of some progressive renal diseases. Pharmacological characterization and molecular cloning of All receptor reveals at least two major subtypes of All receptors, AT 1 and AT 2 , in the kidney and other tissues. the AT 1 receptor cDNA encodes a 359 amino acid protein with structure typical of seven transmembrane G‐protein coupled receptors. Two isoforms of AT 1 receptor, AT 1A and AT 1B , are known in rodents, but probably only one occurs in other mammals including humans. the AT 2 receptor cDNA, a 363 amino acid protein, shares only 32% identical amino acid residues with AT 1 receptor, although it also has a seven transmembrane domain topology. In adult mammalian kidneys, AT 1 receptors predominate in the glomerular mesangium, proximal tubular epithelium, renomedullary interstitial cells in the inner stripe of the outer medulla and large preglomerular vessels except those in human and monkey where AT 2 receptors predominate. By contrast, in foetal kidneys, AT 2 receptors are the major subtype; however, this shows dramatic regulation during development. Physiological studies using AT 1 selective antagonists show that the known actions of All on renal haemodynamics, glomerular filtration, and tubular sodium and water transport are mediated by this subtype of All receptors. In addition, AT 1 receptors also mediate hypertrophic and mitogenic actions of All on cultured glomerular mesangial cells and proximal tubular epithelial cells, and on extra‐cellular matrix accumulation in animal models of progressive renal diseases. By contrast, blockade of AT 2 receptors has no effect on renal haemodynamics, tubular sodium reabsorption or growth properties of All. Overall, All exerts multiple actions in the kidney by interacting with different subtypes of All receptors located on multiple cellular sites.