Recent advances in angiotensin II signaling

Abstract

Angiotensin II (Ang II) * is a multifunctional hormone that influences the function of cardiovascular cells through a complex series of intracellular signaling events initiated by the interaction of Ang II with AT 1 and AT 2 receptors. AT 1 receptor activation leads to cell growth, vascular contraction, inflammatory responses and salt and water retention, whereas AT 2 receptors induce apoptosis, vasodilation and natriuresis. These effects are mediated via complex, interacting signaling pathways involving stimulation of PLC and Ca 2+ mobilization; activation of PLD, PLA 2 , PKC, MAP kinases and NAD(P)H oxidase, and stimulation of gene transcription. In addition, Ang II activates many intracellular tyrosine kinases that play a role in growth signaling and inflammation, such as Src, Pyk2, p130Cas, FAK and JAK/STAT. These events may be direct or indirect via transactivation of tyrosine kinase receptors, including PDGFR, EGFR and IGFR. Ang II induces a multitude of actions in various tissues, and the signaling events following occupancy and activation of Ang receptors are tightly controlled and extremely complex. Alterations of these highly regulated signaling pathways may be pivotal in structural and functional abnormalities that underlie pathological processes in cardiovascular diseases such as cardiac hypertrophy, hypertension and atherosclerosis.

Angiotensin II Inhibits the ROMK-like Small Conductance K Channel in Renal Cortical Collecting Duct during Dietary Potassium Restriction

“…An early event following AngII binding to the AT1R is activation of phospholipase C (PLC) leading to stimulation of PKC (15). Activation of PKC has previously been reported to inhibit the ROMK channel (21).…”

“…AngII binding to the AT1R induces multiple signaling cascades, including those associated with phospholipids, proteintyrosine phosphorylation, and activation of non-receptor tyrosine kinases, such as cSrc (15). An early event following AT1 receptor activation is PLC-dependent hydrolysis of PIP 2 (15).…”

“…An early event following AT1 receptor activation is PLC-dependent hydrolysis of PIP 2 (15). This is associated with rapid production of inositol 1,4,5-trisphosphate and a more sustained release of diacylglycerol, which are involved in Ca 2ϩ mobilization from internal stores and stimulation of PKC, respectively.…”

“…AngII exerts its physiological effects by binding to AT1 and AT2 receptors. AT1 receptor (AT1R) binding activates a number of signaling molecules, including PKC and PTK (cSrc) (15), whereas the precise nature of the signaling pathways activated by the AT2 receptor are still poorly understood (16). Although the effect of AngII on the ROMK channel is unknown, luminal perfusion of distal tubules with AngII stimulates sodium absorption yet suppresses potassium secretion (17), suggesting that AngII may inhibit apical K channels in the CCD.…”

Expression of AT1 and AT2 angiotensin receptors in astrocytomas is associated with poor prognosis

“…Recent studies have revealed that ANGII also participates in other physiologic processes including cell growth, cell differentiation, and receptor-mediated apoptosis (Stoll et al, 1995;Escobar et al, 2004). AT1 is present in all tissues, whereas AT2 is highly expressed in pathologic conditions such as heart failure and myocardial hypertrophy (Nahmias and Strosberg, 1995;Dzau et al, 2001;Touyz and Berry, 2002). Some reports indicate that ANGII induces neovascularisation (Fernandez et al, 1985;Le Noble et al, 1991;Andrade et al, 1996) due to the upregulation of growth factors such as PDGF (Khachigian et al, 2000;Cook et al, 2002), transforming growth factor-b (Kagami et al, 1994;Ohta et al, 1994;Hamaguchi et al, 1999;Weigert et al, 2002), insulin-like growth factor-1 (Brink et al, 1999;Haddad et al, 2003), basic fibroblast growth factor (Peng et al, 2001), VEGF (Otani et al, 1998;Tamarat et al, 2002), and angiopoietin 2 (Otani et al, 2001).…”