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ANGIOTENSIN II RECEPTORS SUBTYPES MEDIATE DIVERSE GENE EXPRESSION PROFILE IN ADULT HYPERTROPHIC CARDIOMYOCYTES
Author(s) -
Zhou Juan,
Xu Xin,
Liu JinJun,
Lin YuanXi,
Gao GuangDao
Publication year - 2007
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2007.04694.x
Subject(s) - angiotensin ii , receptor , endocrinology , medicine , losartan , angiotensin receptor , biology , protein kinase c , phospholipase c , signal transduction , chemistry , microbiology and biotechnology
SUMMARY1 Although the systemic and cardiac renin–angiotensin systems are known to be activated in the setting of pressure overload, the actions and signalling mechanisms of angiotensin (Ang) II via AT 1 and AT 2 receptors in hypertrophic cardiomyocytes (CM) remain largely unclear. 2 Hypertrophic CM were prepared from rats with aortic banding for 8 weeks, cultured and then treated as follows: (i) 1 µmol/L AngII for 24 h; (ii) 10 µmol/L losartan (an AT 1 receptor antagonist) for 1 h followed by 1 µmol/L AngII for 24 h; and (iii) 10 µmol/L PD123319 (an AT 2 receptor antagonist) for 1 h followed by 1 µmol/L AngII for 24 h. Changes in the expression of genes following stimulation of AT 1 and AT 2 receptors specific to G‐protein‐coupled receptor (GPCR) signalling pathways were tested using GEArray (Superarray, Bethesda, MD, USA). The effects of AngII, acting via AT 1 and AT 2 receptors, on the expression of tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐6 were confirmed by reverse transcription–polymerase chain reaction and radioimmunoassay. 3 The genes regulated via stimulation of AT 1 receptors were mainly restricted to the signalling pathways including cAMP/protein kinase (PK) A, Ca 2+ , PKC, protein tyrosine kinase, mitogen‐activated protein kinases, phosphatidylinositol 3‐kinase and nuclear factor‐κB. In addition to these pathways related to activation of AT 1 receptors, four additional signalling pathways were found to be associated with stimulation of AT 2 receptors, including phospholipase C, nitric oxide/cGMP, Rho and Janus kinase/signal transducer and activator of transcription. Blockade of AT 2 receptors decreased the mRNA and protein expression of TNF‐α and IL‐1β, whereas blockade of AT 1 receptors had no such effect. 4 In conclusion, in hypertrophic CM, AngII leads to distinct signalling responses mediated by AT 1 and AT 2 receptors. Stimulation of AT 2 receptors appears to have a greater influence on GPCR‐signalling than stimulation of AT 1 receptors. Angiotensin II enhances the synthesis and secretion of TNF‐α and IL‐1β in hypertrophic CM, which is mediated by AT 2 , but not AT 1 , receptors.