Expression of glomerular receptor for angiotensin II

Lili Zhou
Division of Nephrology, Nanfang Hospital, Southern Medical University, China

As the vasoactivehormone effector of the renin-angiotensin-aldosterone system (RAAS), angiotensin II (AngII) was first found to induce vasoconstriction of the glomerular capillaries in 1972, suggesting the potential existence of its receptors in glomerular mesangiumHowever, the specific AngII receptors in isolated glomeruliwerenot well characterized until 1974 (2).The AngII receptorsturned out to localize on themesangial cells and induce a contractile response (3)There are two subtypes of AngII receptors, AT1 and AT2. In 1992,using antagonist-inhibited 125I-AngII binding, D. Chansel et al. found that AT1 primarily mediates the vasoconstrictive properties of AngII on mesangial cells throughincreases in intracellular calcium concentration (4).In 1993the localization of AT1 in mesangium was directly visualized by in situ hybridization (5). Subsequently, the more widespread distribution of Ang II receptors,possibly including in podocytes, was hypothesizedby W. Kriz et al.(6)based on data from Yamada et al. (7). The presence of both AT1 and AT2 receptorsin podocytes was subsequentlyverified by Sharma et al. in 1998 (8). AT1 was found to be more abundant (~75%) than AT2 inpodocytes (9)and responsible for structural podocyte damage and cell stress induced by AngII (10). The discovery of AT1 and its function inmesangial cells and podocytes over the last 30 years has led to rationale as to the importance of AngII on glomerular microcirculation and ultrafiltration originally described in 1976 (11). Since then, additionalfunctions of AT1 and AT2 have been elucidated, and the elegant contribution to the coordination and regulation of glomerular functions described

References: 

  1. Hornych H, Beaufils M, Richet G.The effect of exogenous angiotensin on superficial and deep glomeruli in the rat kidney.Kidney Int. 1972 Dec;2(6):336-43.
  2. Sraer JD, Sraer J, Ardaillou R, Mimoune O.Evidence for renal glomerular receptors for angiotensin II.Kidney Int. 1974 Oct;6(4):241-6.
  3. Foidart J, Sraer J, Delarue F, Mahieu P, Ardaillou R.Evidence for mesangial glomerular receptors for angiotensin II linked to mesangial cell contractility.FEBS Lett. 1980 Dec 1;121(2):333-9.
  4. Chansel D, Czekalski S, Pham P, Ardaillou R.Characterization of angiotensin II receptor subtypes in human glomeruli and mesangial cells.Am J Physiol. 1992 Mar;262(3 Pt 2):F432-41.
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  6. Kriz W, Hackenthal E, Nobiling R, Sakai T, Elger M, Hähnel B.A role for podocytes to counteract capillary wall distension.Kidney Int. 1994 Feb;45(2):369-76.
  7. Yamada H, Sexton PM, Chai SY, Adam WR, Mendelsohn FA.Angiotensin II receptors in the kidney. Localization and physiological significance.Am J Hypertens. 1990 Mar;3(3):250-5.
  8. Sharma M, Sharma R, Greene AS, McCarthy ET, Savin VJ.Documentation of angiotensin II receptors in glomerular epithelial cells.Am J Physiol. 1998 Mar;274(3 Pt 2):F623-7.
  9. Wang L, Flannery PJ, Spurney RF.Characterization of angiotensin II-receptor subtypes in podocytes.J Lab Clin Med. 2003 Nov;142(5):313-21.
  10. Hoffmann S, Podlich D, Hähnel B, Kriz W, Gretz N.Angiotensin II type 1 receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats.J Am Soc Nephrol. 2004 Jun;15(6):1475-87.
  11. Blantz RC, Konnen KS, Tucker BJ.Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat.J Clin Invest. 1976 Feb;57(2):419-34.

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